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Structural Reconstruction of Protein-Protein Complexes Involved in Intracellular Signaling

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Advanced Technologies for Protein Complex Production and Characterization

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 896))

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Abstract

Signaling complexes within the cell convert extracellular cues into physiological outcomes. Their assembly involves signaling enzymes, allosteric regulators and scaffold proteins that often contain long stretches of disordered protein regions, display multi-domain architectures, and binding affinity between individual components is low. These features are indispensable for their central roles as dynamic information processing hubs, on the other hand they also make reconstruction of structurally homogeneous complex samples highly challenging. In this present chapter we discuss protein machinery which influences extracellular signal reception, intracellular pathway activity, and cytoskeletal or transcriptional activity.

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References

  1. Kobilka BK (2007) G protein coupled receptor structure and activation. Biochim Biophys Acta 1768(4):794–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289(5480):739–745

    Article  CAS  PubMed  Google Scholar 

  3. Yin X, Xu H, Hanson M, Liu W (2014) GPCR crystallization using lipidic cubic phase technique. Curr Pharm Biotechnol 15(10):971–979

    Article  CAS  PubMed  Google Scholar 

  4. Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450(7168):383–387

    Article  CAS  PubMed  Google Scholar 

  5. Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007) GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318(5854):1266–1273

    Article  CAS  PubMed  Google Scholar 

  6. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS, Choi H-J, 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(5854):1258–1265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, Chae PS, Devree BT, Rosenbaum DM, Thian FS, Kobilka TS, Schnapp A, Konetzki I, Sunahara RK, Gellman SH, Pautsch A, Steyaert J, Weis WI, Kobilka BK (2011) Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor. Nature 469(7329):175–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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(7366):549–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zaidel-Bar R, Itzkovitz S, Ma’ayan A, Iyengar R, Geiger B (2007) Functional atlas of the integrin adhesome. Nat Cell Biol 9(8):858–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Deakin NO, Pignatelli J, Turner CE (2012) Diverse roles for the paxillin family of proteins in cancer. Genes Cancer 3(5–6):362–370

    Article  PubMed  PubMed Central  Google Scholar 

  11. Deramaudt TB, Dujardin D, Noulet F, Martin S, Vauchelles R, Takeda K, Ronde P (2014) Altering FAK-paxillin interactions reduces adhesion, migration and invasion processes. PLoS ONE 9(3):e92059

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wang Y, Chien S (2007) Analysis of integrin signaling by fluorescence resonance energy transfer. Methods Enzymol 426:177–201

    Article  CAS  PubMed  Google Scholar 

  13. Patla I, Volberg T, Elad N, Hirschfeld-Warneken V, Grashoff C, Fassler R, Spatz JP, Geiger B, Medalia O (2010) Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography. Nat Cell Biol 12(9):909–915

    Article  CAS  PubMed  Google Scholar 

  14. Calderwood DA, Zent R, Grant R, Rees DJ, Hynes RO, Ginsberg MH (1999) The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation. J Biol Chem 274(40):28071–28074

    Article  CAS  PubMed  Google Scholar 

  15. Wegener KL, Campbell ID (2008) Transmembrane and cytoplasmic domains in integrin activation and protein-protein interactions (review). Mol Membr Biol 25(5):376–387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Legate KR, Fassler R (2009) Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails. J Cell Sci 122(Pt 2):187–198

    Article  CAS  PubMed  Google Scholar 

  17. Schaller MD (2010) Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci 123(Pt 7):1007–1013

    Article  CAS  PubMed  Google Scholar 

  18. Bertolucci CM, Guibao CD, Zheng J (2005) Structural features of the focal adhesion kinase-paxillin complex give insight into the dynamics of focal adhesion assembly. Protein Sci 14(3):644–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ginsberg MH, Partridge A, Shattil SJ (2005) Integrin regulation. Curr Opin Cell Biol 17(5):509–516

    Article  CAS  PubMed  Google Scholar 

  20. Bhattacharyya RP, Remenyi A, Yeh BJ, Lim WA (2006) Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits. Annu Rev Biochem 75:655–680

    Article  CAS  PubMed  Google Scholar 

  21. Good MC, Zalatan JG, Lim WA (2011) Scaffold proteins: hubs for controlling the flow of cellular information. Science 332(6030):680–686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bardwell L (2004) A walk-through of the yeast mating pheromone response pathway. Peptides 25(9):1465–1476

    Article  CAS  PubMed  Google Scholar 

  23. Good M, Tang G, Singleton J, Remenyi A, Lim WA (2009) The Ste5 scaffold directs mating signaling by catalytically unlocking the Fus3 MAP kinase for activation. Cell 136(6):1085–1097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zalatan JG, Coyle SM, Rajan S, Sidhu SS, Lim WA (2012) Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation. Science 337(6099):1218–1222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Dhanasekaran DN, Kashef K, Lee CM, Xu H, Reddy EP (2007) Scaffold proteins of MAP-kinase modules. Oncogene 26(22):3185–3202

    Article  CAS  PubMed  Google Scholar 

  26. Brennan DF, Dar AC, Hertz NT, Chao WCH, Burlingame AL, Shokat KM, Barford D (2011) A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. Nature 472(7343):366–369

    Article  CAS  PubMed  Google Scholar 

  27. Dos Remedios CG, Chhabra D, Kekic M, Dedova IV, Tsubakihara M, Berry DA, Nosworthy NJ (2003) Actin binding proteins: regulation of cytoskeletal microfilaments. Physiol Rev 83(2):433–473

    Article  PubMed  Google Scholar 

  28. Goley ED, Welch MD (2006) The ARP2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol 7(10):713–726

    Article  CAS  PubMed  Google Scholar 

  29. Rohatgi R, Ma L, Miki H, Lopez M, Kirchhausen T, Takenawa T, Kirschner MW (1999) The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97(2):221–231

    Article  CAS  PubMed  Google Scholar 

  30. Volkmann N, Amann KJ, Stoilova-McPhie S, Egile C, Winter DC, Hazelwood L, Heuser JE, Li R, Pollard TD, Hanein D (2001) Structure of Arp2/3 complex in its activated state and in actin filament branch junctions. Science 293(5539):2456–2459

    Article  CAS  PubMed  Google Scholar 

  31. Gournier H, Goley ED, Niederstrasser H, Trinh T, Welch MD (2001) Reconstitution of human Arp2/3 complex reveals critical roles of individual subunits in complex structure and activity. Mol Cell 8(5):1041–1052

    Article  CAS  PubMed  Google Scholar 

  32. Robinson RC, Turbedsky K, Kaiser DA, Marchand JB, Higgs HN, Choe S, Pollard TD (2001) Crystal structure of Arp2/3 complex. Science 294(5547):1679–1684

    Article  CAS  PubMed  Google Scholar 

  33. Beltzner CC, Pollard TD (2004) Identification of functionally important residues of Arp2/3 complex by analysis of homology models from diverse species. J Mol Biol 336(2):551–565

    Article  CAS  PubMed  Google Scholar 

  34. Goley ED, Rodenbusch SE, Martin AC, Welch MD (2004) Critical conformational changes in the Arp2/3 complex are induced by nucleotide and nucleation promoting factor. Mol Cell 16(2):269–279

    Article  CAS  PubMed  Google Scholar 

  35. Egile C, Rouiller I, Xu XP, Volkmann N, Li R, Hanein D (2005) Mechanism of filament nucleation and branch stability revealed by the structure of the Arp2/3 complex at actin branch junctions. PLoS Biol 3(11):e383

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rodal AA, Sokolova O, Robins DB, Daugherty KM, Hippenmeyer S, Riezman H, Grigorieff N, Goode BL (2005) Conformational changes in the Arp2/3 complex leading to actin nucleation. Nat Struct Mol Biol 12(1):26–31

    Article  CAS  PubMed  Google Scholar 

  37. Berger I, Blanco AG, Boelens R, Cavarelli J, Coll M, Folkers GE, Nie Y, Pogenberg V, Schultz P, Wilmanns M, Moras D, Poterszman A (2011) Structural insights into transcription complexes. J Struct Biol 175(2):135–146

    Article  CAS  PubMed  Google Scholar 

  38. Kandiah E, Trowitzsch S, Gupta K, Haffke M, Berger I (2014) More pieces to the puzzle: recent structural insights into class II transcription initiation. Curr Opin Struct Biol 24:91–97

    Article  CAS  PubMed  Google Scholar 

  39. Tsai K-L, Tomomori-Sato C, Sato S, Conaway RC, Conaway JW, Asturias FJ (2014) Subunit architecture and functional modular rearrangements of the transcriptional mediator complex. Cell 157(6):1430–1444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lewis BA (2010) Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex. J Cell Sci 123(Pt 2):159–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Poss ZC, Ebmeier CC, Taatjes DJ (2013) The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol 48(6):575–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Carlsten JO, Zhu X, Gustafsson CM (2013) The multitalented Mediator complex. Trends Biochem Sci 38(11):531–537

    Article  CAS  PubMed  Google Scholar 

  43. Meyer KD, Lin S-C, Bernecky C, Gao Y, Taatjes DJ (2010) p53 activates transcription by directing structural shifts in Mediator. Nat Struct Mol Biol 17(6):753–760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bieniossek C, Papai G, Schaffitzel C, Garzoni F, Chaillet M, Scheer E, Papadopoulos P, Tora L, Schultz P, Berger I (2013) The architecture of human general transcription factor TFIID core complex. Nature 493(7434):699–702

    Article  CAS  PubMed  Google Scholar 

  45. Cianfrocco MA, Kassavetis GA, Grob P, Fang J, Juven-Gershon T, Kadonaga JT, Nogales E (2013) Human TFIID binds to core promoter DNA in a reorganized structural state. Cell 152(1–2):120–131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. He Y, Fang J, Taatjes DJ, Nogales E (2013) Structural visualization of key steps in human transcription initiation. Nature 495(7442):481–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41(Database issue):D808–D815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sahl SJ, Moerner WE (2013) Super-resolution fluorescence imaging with single molecules. Curr Opin Struct Biol 23(5):778–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR (1997) Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science 278(5345):1907–1916

    Article  CAS  PubMed  Google Scholar 

  50. McCudden CR, Hains MD, Kimple RJ, Siderovski DP, Willard FS (2005) G-protein signaling: back to the future. Cell Mol Life Sci 62(5):551–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ikeda SR (1996) Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits. Nature 380(6571):255–258

    Article  CAS  PubMed  Google Scholar 

  52. Bernecky C, Taatjes DJ (2012) Activator-mediator binding stabilizes RNA polymerase II orientation within the human mediator-RNA polymerase II-TFIIF assembly. J Mol Biol 417(5):387–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by a “Lendület” Grant from the Hungarian Academy of Sciences (LP2013-57) and by the Hungarian Research Fund (OTKA NN 114309).

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Authors and Affiliations

  1. MTA “Lendület” Protein Interaction Group, Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary

    Klára Kirsch, Péter Sok & Attila Reményi

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  1. Klára Kirsch
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  2. Péter Sok
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  3. Attila Reményi
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Correspondence to Attila Reményi .

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Editors and Affiliations

  1. Center for Biological Research, SpanishNationalResearchCouncil(CIB-CSIC), Madrid, Spain

    M. Cristina Vega

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Kirsch, K., Sok, P., Reményi, A. (2016). Structural Reconstruction of Protein-Protein Complexes Involved in Intracellular Signaling. In: Vega, M. (eds) Advanced Technologies for Protein Complex Production and Characterization. Advances in Experimental Medicine and Biology, vol 896. Springer, Cham. https://doi.org/10.1007/978-3-319-27216-0_20

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