Skip to main content
SpringerLink
Log in
Book cover

Disruption of Protein-Protein Interfaces pp 113–134Cite as

Protein–Protein Interactions in the Solid State: The Troubles of Crystallizing Protein–Protein Complexes

  • Chapter
  • First Online:

  • 809 Accesses

Abstract

The determination of the tri-dimensional structure of protein-protein interfaces is an important step for every research program aimed to the discovery of molecules able to interfere with protein-protein interactions. The main issue regarding the structure determination by X-ray crystallography of protein-protein interfaces and of the interactions with molecules able to interfere or regulate such interactions, deals with the ability to obtain such complexes in the crystalline state. This chapter deals with the experimental problems related to obtaining pure proteins and protein complexes and their crystallization strategies. Selected examples from the literature are provided.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Notes

  1. 1.

    The attempt to satisfy the evident need to couple structural data and thermodynamic parameters of protein–protein complexes has been undertaken by compiling the protein–protein interactions thermodynamic (PINT) database (http://www.bioinfodatabase.com/pint/index.html) [34]. PINT reports experimental data of protein–protein interactions such as dissociation constant (Kd), association constant (Ka), free energy change (ΔG), enthalpy change (ΔH), and heat capacity change (ΔCp) associated with the protein sequence and structure. Also, the experimental methods and the related literature are available. The PINT database is a unique tool as it provides the possibility to understand the factors that determine protein–protein interactions and their specificity.

References

  1. Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J 27:336–349

    Article  CAS  Google Scholar 

  2. Allison AC (2009) Genetic control of resistance to human malaria. Curr Opin Immunol 21:499–505

    Article  CAS  Google Scholar 

  3. Perrakis A, Musacchio A, Cusack S, Petosa C (2011) Investigating a macromolecular complex: the toolkit of methods. J Struct Biol 175:106–112

    Article  CAS  Google Scholar 

  4. Benvenuti M, Mangani S (2007) Crystallization of soluble proteins in vapor diffusion for x-ray crystallography. Nat Protoc 2:1633–1651

    Article  CAS  Google Scholar 

  5. Terwilliger TC, Stuart D, Yokoyama S (2009) Lessons from structural genomics. Ann Rev Biophys 38:371–383

    Article  CAS  Google Scholar 

  6. Goodsell DS, Olson AJ (2000) Structural symmetry and protein function. Annu Rev Biophys Biomol Struct 29:105–153

    Article  CAS  Google Scholar 

  7. Henrick K, Thornton JM (1998) PQS: a protein quaternary structure file server. Trends Biochem Sci 23:358–361

    Article  CAS  Google Scholar 

  8. Taylor JP, Hardy J, Fischbeck KH (2002) Toxic proteins in neurodegenerative disease. Science 296:1991–1995

    Article  CAS  Google Scholar 

  9. Ponstingl H, Henrick K, Thornton JM (2000) Discriminating between homodimeric and monomeric proteins in the crystalline state. Proteins 41:47–57

    Article  CAS  Google Scholar 

  10. Ponstingl H, Kabir T, Thornton JM (2003) Automatic inference of protein quaternary structure from crystals. J Appl Crystallogr 36:1116–1122

    Article  CAS  Google Scholar 

  11. Krissinel E, Henrick K (2007) Protein interfaces, surfaces and assemblies service PISA at European Bioinformatics Institute, http://www.ebi.ac.uk/msd-srv/prot_int/pistart.html

  12. Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372:774–797

    Article  CAS  Google Scholar 

  13. Krissinel E (2011) Macromolecular complexes in crystals and solutions. Acta Crystallogr D Biol Crystallogr 67:376–385

    Article  CAS  Google Scholar 

  14. Zimmerman SB, Minton AP (1993) Macromolecular crowding: biochemical, biophysical, and physiological consequences. Annu Rev Biophys Biomol Struct 22:27–65

    Article  CAS  Google Scholar 

  15. Minton AP (2001) The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J Biol Chem 276:10577–10580

    Article  CAS  Google Scholar 

  16. Ellis RJ (2001) Macromolecular crowding: obvious but underappreciated. Trends Biochem Sci 26:597–604

    Article  CAS  Google Scholar 

  17. Bertini I, Gray HB, Stiefel E, Valentine JS (2007) Biological inorganic chemistry structure and reactivity University Science Books. Sausalito, CA

    Google Scholar 

  18. Tottey S, Harvie DR, Robinson NJ (2005) Understanding how cells allocate metals using metal sensors and metallochaperones. Acc Chem Res 38:775–783

    Article  CAS  Google Scholar 

  19. Maret W (2009) Molecular aspects of human cellular zinc homeostasis: redox control of zinc potentials and zinc signals. Biometals 22:149–157

    Article  CAS  Google Scholar 

  20. Fujinaga M, James MN (1987) Rat submaxillary gland serine protease, tonin: structure solution and refinement at 1.8 Å resolution. J Mol Biol 195(2):373–396

    Article  CAS  Google Scholar 

  21. Banci L, Bertini I, Calderone V, Cramaro F, Del Conte R, Fantoni A, Mangani S, Quattrone A, Viezzoli MS (2005) A prokaryotic superoxide dismutase paralog lacking two Cu ligands: from largely unstructured in solution to ordered in the crystal. Proc Natl Acad Sci USA 102:7541–7546

    Article  CAS  Google Scholar 

  22. Jaffe EK (2005) Morpheeins: a new structural paradigm for allosteric regulation. Trends Biochem Sci 30:490–497

    Article  CAS  Google Scholar 

  23. Jaffe EK (2010) Morpheeins: a new pathway for allosteric drug discovery. Open Conf Proc J 1:1–6

    Article  CAS  Google Scholar 

  24. Jaffe EK, Lawrence SH (2012) The morpheein model of allostery: evaluating proteins as potential morpheeins. Methods Mol Biol 796:217–231

    Article  CAS  Google Scholar 

  25. Lawrence SH, Jaffe EK (2008) Expanding the concepts in protein structure-function relationships and enzyme kinetics: teaching using morpheeins. Biochem Mol Biol Educ 36:274–283

    Article  CAS  Google Scholar 

  26. Selwood T, Jaffe EK (2012) Dynamic dissociating homo-oligomers and the control of protein function. Arch Biochem Biophys 519:131–143

    Article  CAS  Google Scholar 

  27. Lawrence SH, Ramirez UD, Tang L, Fazliyez F, Kundrat L, Markham GD, Jaffe EK (2008) Shape shifting leads to small-molecule allosteric drug discovery. Chem Biol 15:586–596

    Article  CAS  Google Scholar 

  28. Howard J, Hyman AA (2003) Dynamics and mechanics of the microtubule plus end. Nature 422:753–758

    Article  CAS  Google Scholar 

  29. Small JV, Kaverina I (2003) Microtubules meet substrate adhesions to arrange cell polarity. Curr Opin Cell Biol 15:40–47

    Article  CAS  Google Scholar 

  30. Mitchison TJ (1993) Localization of an exchangeable GTP binding site at the plus end of microtubules. Science 261:1044–1047

    Article  CAS  Google Scholar 

  31. Desai A, Mitchison TJ (1997) Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 13:83–117

    Article  CAS  Google Scholar 

  32. Nogales E, Whittaker M, Milligan RA, Downing KH (1999) High-resolution model of the microtubule. Cell 96:79–88

    Article  CAS  Google Scholar 

  33. Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M (2004) Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428:198–202

    Article  CAS  Google Scholar 

  34. Kumar MD, Gromiha MM (2006) PINT: protein-protein interactions thermodynamic database. Nucleic Acids Res 34:D195–D198

    Article  CAS  Google Scholar 

  35. Tung M, Gallagher DT (2009) The biomolecular crystallization database version 4: expanded content and new features. Acta Crystallogr D Biol Crystallogr 65:18–23

    Article  CAS  Google Scholar 

  36. Grigorieff N, Harrison SC (2011) Near-atomic resolution reconstructions of icosahedral viruses from electron cryo-microscopy. Curr Opin Struct Biol 21:265–273

    Article  CAS  Google Scholar 

  37. Lupetti P (2005) Cryotechniques for electron microscopy: a mini review. In: From Cells to Protein: Imaging Nature across Dimensions, Springer, Dordrecht, pp 53–70

    Google Scholar 

  38. Zhang X, Settembre E, Xu C, Dormitzer PR, Bellamy R, Harrison SC, Grigorieff N (2008) Near-atomic resolution using electron cryomicroscopy and single-particle reconstruction. Proc Natl Acad Sci USA 105:1867–1872

    Article  CAS  Google Scholar 

  39. Zhou ZH (2008) Towards atomic resolution structural determination by single-particle cryo-electron microscopy. Curr Opin Struct Biol 18:218–228

    Article  CAS  Google Scholar 

  40. Jonic S, Venien-Bryan C (2009) Protein structure determination by electron cryo-microscopy. Curr Opin Pharmacol 9:636–642

    Article  CAS  Google Scholar 

  41. Baker ML, Zhang J, Ludtke SJ, Chiu W (2010) Cryo-EM of macromolecular assemblies at near-atomic resolution. Nat Protoc 5:1697–1708

    Article  CAS  Google Scholar 

  42. Zhou ZH (2011) Atomic resolution cryo electron microscopy of macromolecular complexes. Adv Protein Chem Struct Biol 82:1–35

    Article  CAS  Google Scholar 

  43. Ball G, Parton RM, Hamilton RS, Davis I (2012) A cell biologist’s guide to high resolution imaging. Methods Enzymol 504:29–55

    Article  CAS  Google Scholar 

  44. Geerlof A, Brown J, Coutard B, Egloff MP, Enguita FJ, Fogg MJ, Gilbert RJ, Groves MR, Haouz A, Nettleship JE, Nordlund P, Owens RJ, Ruff M, Sainsbury S, Svergun DI, Wilmanns M (2006) The impact of protein characterization in structural proteomics. Acta Crystallogr D Biol Crystallogr 62:1125–1136

    Article  CAS  Google Scholar 

  45. Banci L, Bertini I, Mangani S (2005) Integration of XAS and NMR techniques for the structure determination of metalloproteins: examples from the study of copper transport proteins. J Synchrotron Radiat 12:94–97

    Article  CAS  Google Scholar 

  46. Strange RW, Feiters MC (2008) Biological X-ray absorption spectroscopy (BioXAS): a valuable tool for the study of trace elements in the life sciences. Curr Opin Struct Biol 18:609–616

    Article  CAS  Google Scholar 

  47. Banci L, Bertini I, Del Conte R, Mangani S, Meyer-Klaucke W (2003) X-ray absorption and NMR spectroscopic studies of CopZ, a copper chaperone in Bacillus subtilis: the coordination properties of the copper ion. Biochemistry 42:2467–2474

    Article  CAS  Google Scholar 

  48. Phelps RA, Cann JR (1957) Effect of binding of ions and other small molecules on protein structure. III. Influence of amino acids on the isomerization of proteins. J Am Chem Soc 79:4677–4679

    Article  CAS  Google Scholar 

  49. Fegan A, White B, Carlson JCT, Wagner CR (2010) Chemically controlled protein assembly: techniques and applications. Chem Rev 110:3315–3336

    Article  CAS  Google Scholar 

  50. Nooren IM, Thornton JM (2003) Diversity of protein–protein interactions. EMBO J 22:3486–3492

    Article  CAS  Google Scholar 

  51. Cardinale D, Salo-Ahen OM, Ferrari S, Ponterini G, Cruciani G, Carosati E, Tochowicz AM, Mangani S, Wade RC, Costi MP (2010) Homodimeric enzymes as drug targets. Curr Med Chem 17:826–846

    Article  CAS  Google Scholar 

  52. Xu X, Song Y, Li Y, Chang J, Zhang H, An L (2010) The tandem affinity purification method: an efficient system for protein complex purification and protein interaction identification. Protein Expr Purif 72:149–156

    Article  CAS  Google Scholar 

  53. Li Y (2011) The tandem affinity purification technology: an overview. Biotechnol Lett 33:1487–1499

    Article  CAS  Google Scholar 

  54. Williamson MP, Sutcliffe MJ (2010) Protein-protein interactions. Biochem Soc Trans 38:875–878

    Article  CAS  Google Scholar 

  55. Kerrigan JJ, Xie Q, Ames RS, Lu Q (2011) Production of protein complexes via co-expression. Protein Expr Purif 75:1–14

    Article  CAS  Google Scholar 

  56. Zhao Y, Bishop B, Clay JE, Lu W, Jones M, Daenke S, Siebold C, Stuart DI, Yvonne Jones E, Radu Aricescu A (2011) Automation of large scale transient protein expression in mammalian cells. J Struct Biol 175:209–215

    Article  CAS  Google Scholar 

  57. Vijayachandran LS, Viola C, Garzoni F, Trowitzsch S, Bieniossek C, Chaillet M, Schaffitzel C, Busso D, Romier C, Poterszman A, Richmond TJ, Berger I (2011) Robots, pipelines, polyproteins: enabling multiprotein expression in prokaryotic and eukaryotic cells. J Struct Biol 175:198–208

    Article  CAS  Google Scholar 

  58. Perrakis A, Romier C (2008) Assembly of protein complexes by coexpression in prokaryotic and eukaryotic hosts: an overview. Methods Mol Biol 426:247–256

    Article  CAS  Google Scholar 

  59. Busso D, Peleg Y, Heidebrecht T, Romier C, Jacobovitch Y, Dantes A, Salim L, Troesch E, Schuetz A, Heinemann U, Folkers GE, Geerlof A, Wilmanns M, Polewacz A, Quedenau C, Büssow K, Adamson R, Blagova E, Walton J, Cartwright JL, Bird LE, Owens RJ, Berrow NS, Wilson KS, Sussman JL, Perrakis A, Celie PHN (2011) Expression of protein complexes using multiple Escherichia coli protein co-expression systems: a benchmarking study. J Struct Biol 175:159–170

    Article  CAS  Google Scholar 

  60. Bieniossek C, Nie Y, Frey D, Olieric N, Schaffitzel C, Collinson I, Romier C, Berger P, Richmond TJ, Steinmetz MO, Berger I (2009) Automated unrestricted multigene recombineering for multiprotein complex production. Nat Methods 6:447–450

    Article  CAS  Google Scholar 

  61. Romier C, Ben JM, Albeck S, Buchwald G, Busso D, Celie PH, Christodoulou E, De M, van GS, Knipscheer P, Lebbink JH, Notenboom V, Poterszman A, Rochel N, Cohen SX, Unger T, Sussman JL, Moras D, Sixma TK, Perrakis A (2006) Co-expression of protein complexes in prokaryotic and eukaryotic hosts: experimental procedures, database tracking and case studies. Acta Crystallogr D Biol Crystallogr 62:1232–1242

    Article  CAS  Google Scholar 

  62. Passon DM, Lee M, Fox AH, Bond CS (2011) Crystallization of a paraspeckle protein PSPC1-NONO heterodimer. Acta Crystallogr Sect F 67:1231–1234

    Article  CAS  Google Scholar 

  63. Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS (2012) Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci USA 109:4846–4850

    Article  CAS  Google Scholar 

  64. Lutter R, Abrahams JP, van Raaij MJ, Todd RJ, Lundqvist T, Buchanan SK, Leslie AG, Walker JE (1993) Crystallization of F1-ATPase from bovine heart mitochondria. J Mol Biol 229:787–790

    Article  CAS  Google Scholar 

  65. Leslie AG, Abrahams JP, Braig K, Lutter R, Menz RI, Orriss GL, van Raaij MJ, Walker JE (1999) The structure of bovine mitochondrial F1-ATPase: an example of rotary catalysis. Biochem Soc Trans 27:37–42

    CAS  Google Scholar 

  66. Gibbons C, Montgomery MG, Leslie AG, Walker JE (2000) The structure of the central stalk in bovine F(1)-ATPase at 2.4 Å resolution. Nat Struct Biol 7:1055–1061

    Article  CAS  Google Scholar 

  67. Stock D, Leslie AG, Walker JE (1999) Molecular architecture of the rotary motor in ATP synthase. Science 286:1700–1705

    Article  CAS  Google Scholar 

  68. Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S (1996) The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 Å. Science 272:1136–1144

    Article  CAS  Google Scholar 

  69. Xia D, Yu CA, Kim H, Xia JZ, Kachurin AM, Zhang L, Yu L, Deisenhofer J (1997) Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science 277:60–66

    Article  CAS  Google Scholar 

  70. Morth JP, Pedersen BP, Toustrup-Jensen MS, Sorensen TL, Petersen J, Andersen JP, Vilsen B, Nissen P (2007) Crystal structure of the sodium-potassium pump. Nature 450:1043–1049

    Article  CAS  Google Scholar 

  71. Drew D, Froderberg L, Baars L, de Gier JW (2003) Assembly and overexpression of membrane proteins in Escherichia coli. Biochim Biophys Acta 1610:3–10

    Article  CAS  Google Scholar 

  72. Miroux B, Walker JE (1996) Over-production of proteins in Escherichia coli: mutant hosts that allow synthesis of some membrane proteins and globular proteins at high levels. J Mol Biol 260(19):289–298

    Article  CAS  Google Scholar 

  73. Wagner S, Klepsch MM, Schlegel S, Appel A, Draheim R, Tarry M, Högbom M, van Wijk KJ, Slotboom DJ, Persson JO, de Gier JW (2008) Tuning Escherichia coli for membrane protein overexpression. PNAS 105:14371–14376

    Article  CAS  Google Scholar 

  74. Hays FA, Roe-Zurz Z, Li M, Kelly L, Gruswitz F, Sali A, Stroud RM (2009) Ratiocinative screen of eukaryotic integral membrane protein expression and solubilization for structure determination. J Struct Funct Genomics 10:9–16

    Article  CAS  Google Scholar 

  75. Gu S, Rehman S, Wang X, Shevchik VE, Pickersgill RW (2012) Structural and functional insights into the pilotin-secretin complex of the type II secretion system. PLoS Pathog 8:e1002531

    Article  CAS  Google Scholar 

  76. Romes EM, Tripathy A, Slep KC (2012) The Structure of a yeast Dyn2-Nup159 complex and the molecular basis for the dynein light chain: nuclear pore interaction. J Biol Chem 287(19):15862–15873

    Google Scholar 

  77. Su CC, Long F, Zimmermann MT, Rajashankar KR, Jernigan RL, Yu EW (2011) Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 470:558–562

    Article  CAS  Google Scholar 

  78. Su CC, Yang F, Long F, Reyon D, Routh MD, Kuo DW, Mokhtari AK, Van Ornam JD, Rabe KL, Hoy JA, Lee YJ, Rajashankar KR, Yu EW (2009) Crystal structure of the membrane fusion protein CusB from Escherichia coli. J Mol Biol 393:342–355

    Article  CAS  Google Scholar 

  79. Long F, Su CC, Zimmermann MT, Boyken SE, Rajashankar KR, Jernigan RL, Yu EW (2010) Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport. Nature 467:484–488

    Article  CAS  Google Scholar 

  80. O’Halloran TV, Culotta VC (2000) Metallochaperones: an intracellular shuttle service for metal ions. J Biol Chem 275:25057–25060

    Article  Google Scholar 

  81. Arnesano F, Banci L, Bertini I, Ciofi-Baffoni S, Molteni E, Huffman DL, O’Halloran TV (2002) Metallochaperones and metal-transporting ATPases: a comparative analysis of sequences and structures. Genome Res 12:255–271

    Article  CAS  Google Scholar 

  82. Banci L, Bertini I, Cantini F, Felli IC, Gonnelli L, Hadjiliadis N, Pierattelli R, Rosato A, Voulgaris P (2006) The Atx1-Ccc2 complex is a metal-mediated protein–protein interaction. Nat Chem Biol 2:367–368

    Article  CAS  Google Scholar 

  83. Bertini I, Cavallaro G, McGreevy KS (2010) Cellular copper management—a draft user’s guide. Coord Chem Rev 254:506–524

    Article  CAS  Google Scholar 

  84. Lamb AL, Torres AS, O’Halloran TV, Rosenzweig AC (2001) Heterodimeric structure of superoxide dismutase in complex with its metallochaperone. Nat Struct Biol 8:751–755

    Article  CAS  Google Scholar 

  85. Banci L, Bertini I, Calderone V, la-Malva N, Felli IC, Neri S, Pavelkova A, Rosato A (2009) Copper(I)-mediated protein–protein interactions result from suboptimal interaction surfaces. Biochem J 422:37–42

    Article  CAS  Google Scholar 

  86. Noinaj N, Easley NC, Oke M, Mizuno N, Gumbart J, Boura E, Steere AN, Zak O, Aisen P, Tajkhorshid E, Evans RW, Gorringe AR, Mason AB, Steven AC, Buchanan SK (2012) Structural basis for iron piracy by pathogenic Neisseria. Nature 483:53–58

    Article  CAS  Google Scholar 

  87. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le TI, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: AG protein-coupled receptor. Science 289:739–745

    Article  CAS  Google Scholar 

  88. Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM, Shichida Y (2002) Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc Natl Acad Sci USA 99:5982–5987

    Article  CAS  Google Scholar 

  89. Massotte D (2003) G protein-coupled receptor overexpression with the baculovirus—insect cell system: a tool for structural and functional studies. Biochimica et Biophysica Acta (BBA): Biomembr 1610:77–89

    Article  CAS  Google Scholar 

  90. Lanyi JK, Schobert B (2004) Local-global conformational coupling in a heptahelical membrane protein: transport mechanism from crystal structures of the nine states in the bacteriorhodopsin photocycle. Biochemistry 43:3–8

    Article  CAS  Google Scholar 

  91. Lundstrom K (2005) Structural biology of G protein-coupled receptors. Bioorg Med Chem Lett 15:3654–3657

    Article  CAS  Google Scholar 

  92. Lundstrom K (2005) Structural genomics of GPCRs. Trends Biotechnol 23:103–108

    Article  CAS  Google Scholar 

  93. Rasmussen SGF, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VRP, Sanishvili R, Fischetti RF, Schertler GFX, Weis WI, Kobilka BK (2007) Crystal structure of the human [bgr]2 adrenergic G-protein-coupled receptor. Nature 450:383–387

    Article  CAS  Google Scholar 

  94. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318:1258–1265

    Article  CAS  Google Scholar 

  95. Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, Henderson R, Leslie AG, Tate CG, Schertler GF (2008) Structure of a beta1-adrenergic G-protein-coupled receptor. Nature 454:486–491

    Article  CAS  Google Scholar 

  96. Park JH, Scheerer P, Hofmann KP, Choe HW, Ernst OP (2008) Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454:183–187

    Article  CAS  Google Scholar 

  97. Warne T, Serrano-Vega MJ, Tate CG, Schertler GF (2009) Development and crystallization of a minimal thermostabilised G protein-coupled receptor. Protein Expr Purif 65:204–213

    Article  CAS  Google Scholar 

  98. Martin A, Damian M, Laguerre M, Parello J, Pucci B, Serre L, Mary S, Marie J, Baneres JL (2009) Engineering a G protein-coupled receptor for structural studies: stabilization of the BLT1 receptor ground state. Protein Sci 18:727–734

    CAS  Google Scholar 

  99. Kimple AJ, Soundararajan M, Hutsell SQ, Roos AK, Urban DJ, Setola V, Temple BR, Roth BL, Knapp S, Willard FS, Siderovski DP (2009) Structural determinants of G-protein alpha subunit selectivity by regulator of G-protein signaling 2 (RGS2). J Biol Chem 284:19402–19411

    Article  CAS  Google Scholar 

  100. Bokoch MP, Zou Y, Rasmussen SG, Liu CW, Nygaard R, Rosenbaum DM, Fung JJ, Choi HJ, Thian FS, Kobilka TS, Puglisi JD, Weis WI, Pardo L, Prosser RS, Mueller L, Kobilka BK (2010) Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. Nature 463:108–112

    Article  CAS  Google Scholar 

  101. Wacker D, Fenalti G, Brown MA, Katritch V, Abagyan R, Cherezov V, Stevens RC (2010) Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography. J Am Chem Soc 132:11443–11445

    Article  CAS  Google Scholar 

  102. Moukhametzianov R, Warne T, Edwards PC, Serrano-Vega MJ, Leslie AG, Tate CG, Schertler GF (2011) Two distinct conformations of helix 6 observed in antagonist-bound structures of a beta1-adrenergic receptor. Proc Natl Acad Sci USA 108:8228–8232

    Article  CAS  Google Scholar 

  103. Zou Y, Weis WI, Kobilka BK (2012) N-Terminal T4 lysozyme fusion facilitates crystallization of a G protein coupled receptor. PLoS ONE 7:e46039

    Article  CAS  Google Scholar 

  104. Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sanna MG, Han GW, Kuhn P, Rosen H, Stevens RC (2012) Crystal structure of a lipid G protein-coupled receptor. Science 335:851–855

    Article  CAS  Google Scholar 

  105. Hino T, Arakawa T, Iwanari H, Yurugi-Kobayashi T, Ikeda-Suno C, Nakada-Nakura Y, Kusano-Arai O, Weyand S, Shimamura T, Nomura N, Cameron AD, Kobayashi T, Hamakubo T, Iwata S, Murata T (2012) G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody. Nature 482:237–240

    CAS  Google Scholar 

  106. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK (2011) Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477(19):549–555

    Article  CAS  Google Scholar 

  107. Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007) GPCR engineering yields high-resolution structural insights into beta-2-Adrenergic receptor function. Science 318:1266–1273

    Article  CAS  Google Scholar 

  108. Hunte C, Zickermann V, Brandt U (2010) Functional modules and structural basis of conformational coupling in mitochondrial complex I. Science 329:448–451

    Article  CAS  Google Scholar 

  109. Sun F, Huo X, Zhai Y, Wang A, Xu J, Su D, Bartlam M, Rao Z (2005) Crystal structure of mitochondrial respiratory membrane protein complex II. Cell 121:1043–1057

    Article  CAS  Google Scholar 

  110. Lancaster CR, Kroger A, Auer M, Michel H (1999) Structure of fumarate reductase from Wolinella succinogenes at 2.2 Å resolution. Nature 402:377–385

    Article  CAS  Google Scholar 

  111. Iverson TM, Luna-Chavez C, Cecchini G, Rees DC (1999) Structure of the Escherichia coli fumarate reductase respiratory complex. Science 284:1961–1966

    Article  CAS  Google Scholar 

  112. Lange C, Nett JH, Trumpower BL, Hunte C (2001) Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure. EMBO J 20:6591–6600

    Article  CAS  Google Scholar 

  113. Menz RI, Walker JE, Leslie AG (2001) Structure of bovine mitochondrial F(1)-ATPase with nucleotide bound to all three catalytic sites: implications for the mechanism of rotary catalysis. Cell 106:331–341

    Article  CAS  Google Scholar 

  114. Wimberly BT, Brodersen DE, Clemons WM Jr, Morgan-Warren RJ, Carter AP, Vonrhein C, Hartsch T, Ramakrishnan V (2000) Structure of the 30S ribosomal subunit. Nature 407:327–339

    Article  CAS  Google Scholar 

  115. Rabl J, Leibundgut M, Ataide SF, Haag A, Ban N (2011) Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1. Science 331:730–736

    Article  CAS  Google Scholar 

  116. Ban N, Nissen P, Hansen J, Moore PB, Steitz TA (2000) The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science 289:905–920

    Article  CAS  Google Scholar 

  117. Klinge S, Voigts-Hoffmann F, Leibundgut M, Arpagaus S, Ban N (2011) Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6. Science 334:941–948

    Article  CAS  Google Scholar 

  118. Groll M, Ditzel L, Lowe J, Stock D, Bochtler M, Bartunik HD, Huber R (1997) Structure of 20S proteasome from yeast at 2.4 Å resolution. Nature 386:463–471

    Article  CAS  Google Scholar 

  119. Chayen NE (2004) Turning protein crystallisation from an art into a science. Curr Opin Struct Biol 14:577–583

    Article  CAS  Google Scholar 

  120. Chayen NE, Saridakis E (2008) Protein crystallization: from purified protein to diffraction-quality crystal. Nat Methods 5:147–153

    Article  CAS  Google Scholar 

  121. Bolanos-Garcia VM, Chayen NE (2009) New directions in conventional methods of protein crystallization. Prog Biophys Mol Biol 101:3–12

    Article  CAS  Google Scholar 

  122. Nooren IM, Thornton JM (2003) Structural characterisation and functional significance of transient protein–protein interactions. J Mol Biol 325:991–1018

    Article  CAS  Google Scholar 

  123. Russell RB, Alber F, Aloy P, Davis FP, Korkin D, Pichaud M, Topf M, Sali A (2004) A structural perspective on protein–protein interactions. Curr Opin Struct Biol 14:313–324

    Article  CAS  Google Scholar 

  124. Radaev S, Li S, Sun PD (2006) A survey of protein–protein complex crystallizations. Acta Crystallogr D Biol Crystallogr 62:605–612

    Article  CAS  Google Scholar 

  125. Radaev S, Sun PD (2002) Crystallization of protein–protein complexes. J Appl Crystallogr 35:674–676

    Article  CAS  Google Scholar 

  126. Toogood PL (2002) Inhibition of protein–protein association by small molecules: approaches and progress. J Med Chem 45:1543–1558

    Article  CAS  Google Scholar 

  127. Pagliaro L, Felding J, Audouze K, Nielsen SJ, Terry RB, Krog-Jensen C, Butcher S (2004) Emerging classes of protein–protein interaction inhibitors and new tools for their development. Curr Opin Chem Biol 8:442–449

    Article  CAS  Google Scholar 

  128. Bourgeas R, Basse MJ, Morelli X, Roche P (2010) Atomic analysis of protein–protein interfaces with known inhibitors: the 2P2I database. PLoS ONE 5:e9598

    Article  CAS  Google Scholar 

  129. Morelli X, Bourgeas R, Roche P (2011) Chemical and structural lessons from recent successes in protein–protein interaction inhibition (2P2I). Curr Opin Chem Biol 15:475–481

    Article  CAS  Google Scholar 

  130. Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW (1997) Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275:983–986

    Article  CAS  Google Scholar 

  131. Liu Z, Sun C, Olejniczak ET, Meadows RP, Betz SF, Oost T, Herrmann J, Wu JC, Fesik SW (2000) Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature 408:1004–1008

    Article  CAS  Google Scholar 

  132. Agamennone M, Cesari L, Lalli D, Turlizzi E, Del CR, Turano P, Mangani S, Padova A (2010) Fragmenting the S100B–p53 interaction: combined virtual/biophysical screening approaches to identify ligands. ChemMedChem 5:428–435

    Article  CAS  Google Scholar 

  133. Cossu F, Milani M, Mastrangelo E, Vachette P, Servida F, Lecis D, Canevari G, Delia D, Drago C, Rizzo V, Manzoni L, Seneci P, Scolastico C, Bolognesi M (2009) Structural basis for bivalent Smac-mimetics recognition in the IAP protein family. J Mol Biol 392:630–644

    Article  CAS  Google Scholar 

  134. Lee EF, Czabotar PE, Smith BJ, Deshayes K, Zobel K, Colman PM, Fairlie WD (2007) Crystal structure of ABT-737 complexed with Bcl-xL: implications for selectivity of antagonists of the Bcl-2 family. Cell Death Differ 14:1711–1713

    Article  CAS  Google Scholar 

  135. He MM, Smith AS, Oslob JD, Flanagan WM, Braisted AC, Whitty A, Cancilla MT, Wang J, Lugovskoy AA, Yoburn JC, Fung AD, Farrington G, Eldredge JK, Day ES, Cruz LA, Cachero TG, Miller SK, Friedman JE, Choong IC, Cunningham BC (2005) Small-molecule inhibition of TNF-alpha. Science 310:1022–1025

    Article  CAS  Google Scholar 

  136. Silvian LF, Friedman JE, Strauch K, Cachero TG, Day ES, Qian F, Cunningham B, Fung A, Sun L, Shipps GW, Su L, Zheng Z, Kumaravel G, Whitty A (2011) Small molecule inhibition of the TNF family cytokine CD40 ligand through a subunit fracture mechanism. ACS Chem Biol 6:636–647

    Article  CAS  Google Scholar 

  137. Cardinale D, Guaitoli G, Tondi D, Luciani R, Henrich S, Salo-Ahen OM, Ferrari S, Marverti G, Guerrieri D, Ligabue A, Frassineti C, Pozzi C, Mangani S, Fessas D, Guerrini R, Ponterini G, Wade RC, Costi MP (2011) Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase. Proc Natl Acad Sci USA 108:E542–E549

    Article  CAS  Google Scholar 

  138. Thangudu RR, Tyagi M, Shoemaker BA, Bryant SH, Panchenko AR, Madej T (2010) Knowledge-based annotation of small molecule binding sites in proteins. BMC Bioinform 11:365

    Article  CAS  Google Scholar 

  139. Shoemaker BA, Zhang D, Tyagi M, Thangudu RR, Fong JH, Marchler-Bauer A, Bryant SH, Madej T, Panchenko AR (2012) IBIS (inferred biomolecular interaction server) reports, predicts and integrates multiple types of conserved interactions for proteins. Nucleic Acids Res 40:D834–D840

    Article  CAS  Google Scholar 

  140. Dynek JN, Vucic D (2010) Antagonists of IAP proteins as cancer therapeutics. Cancer Lett 332(2):206–214

    Google Scholar 

  141. Fulda S, Vucic D (2012) Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov 11:109–124

    Article  CAS  Google Scholar 

  142. Wilson WH, O’Connor OA, Czuczman MS, LaCasce AS, Gerecitano JF, Leonard JP, Tulpule A, Dunleavy K, Xiong H, Chiu YL, Cui Y, Busman T, Elmore SW, Rosenberg SH, Krivoshik AP, Enschede SH, Humerickhouse RA (2010) Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol 11:1149–1159

    Article  CAS  Google Scholar 

  143. Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, Carney DA, He SZ, Huang DC, Xiong H, Cui Y, Busman TA, McKeegan EM, Krivoshik AP, Enschede SH, Humerickhouse R (2012) Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol 30:488–496

    Article  CAS  Google Scholar 

  144. Rudin CM, Hann CL, Garon EB, de Ribeiro OM, Bonomi PD, Camidge DR, Chu Q, Giaccone G, Khaira D, Ramalingam SS, Ranson MR, Dive C, McKeegan EM, Chyla BJ, Dowell BL, Chakravartty A, Nolan CE, Rudersdorf N, Busman TA, Mabry MH, Krivoshik AP, Humerickhouse RA, Shapiro GI, Gandhi L (2012) Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res 18:3163–3169

    Article  CAS  Google Scholar 

  145. Weber L (2010) Patented inhibitors of p53-Mdm2 interaction (2006–2008). Expert Opin Ther Pat 20:179–191

    Article  CAS  Google Scholar 

  146. Millard M, Pathania D, Grande F, Xu S, Neamati N (2011) Small-molecule inhibitors of p53-MDM2 interaction: the 2006–2010 update. Curr Pharm Des 17:536–559

    Article  CAS  Google Scholar 

  147. Warner WA, Sanchez R, Dawoodian A, Li E, Momand J (2012) Identification of FDA-approved drugs that computationally Bind to MDM2. Chem Biol Drug Des 80:631–637

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy

    Stefano Mangani

Authors
  1. Stefano Mangani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefano Mangani .

Editor information

Editors and Affiliations

  1. , Department of Biotechnology, Chemistry a, University of Siena, Siena, Siena, I-53100, Italy

    Stefano Mangani

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Mangani, S. (2013). Protein–Protein Interactions in the Solid State: The Troubles of Crystallizing Protein–Protein Complexes. In: Mangani, S. (eds) Disruption of Protein-Protein Interfaces. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37999-4_5

Download citation

Publish with us

Policies and ethics

Search

Navigation