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Secondary and Supersecondary Structure of Proteins in Light of the Structure of Hydrophobic Cores

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Protein Supersecondary Structures

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1958))

Abstract

The traditional classification of protein structures (with regard to their supersecondary and tertiary conformation) is based on an assessment of conformational similarities between various polypeptide chains and particularly on the presence of specific secondary structural motifs. Mutual relations between secondary folds determine the overall shape of the protein and may be used to assign proteins to specific families (such as the immunoglobulin-like family). An alternative means of conducting structural assessment focuses on the structure of the protein’s hydrophobic core. In this case, the protein is treated as a quasi-micelle, which exposes hydrophilic residues on its surface while internalizing hydrophobic residues. The accordance between the actual distribution of hydrophobicity in a protein and its corresponding theoretical (“idealized”) distribution can be determined quantitatively, which, in turn, enables comparative analysis of structures regarded as geometrically similar (as well as geometrically divergent structures which are nevertheless regarded as similar in the sense of the fuzzy oil drop model). In this scope, the protein may be compared to an “intelligent micelle,” where local disorder is often intentional and related to biological function—unlike traditional surfactant micelles which remain highly symmetrical throughout and do not carry any encoded information.

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References

  1. Sillitoe I, Lewis TE, Cuff AL, Das S, Ashford P, Dawson NL, Furnham N, Laskowski RA, Lee D, Lees J, Lehtinen S, Studer R, Thornton JM, Orengo CA (2015) CATH: comprehensive structural and functional annotations for genome sequences. Nucleic Acids Res 43:D376–D381. https://doi.org/10.1093/nar/gku947

    Article  CAS  PubMed  Google Scholar 

  2. http://www.cathdb.info/

  3. Fox NK, Brenner SE, Chandonia JM (2014) SCOPe: Structural Classification of Proteins—extended, integrating SCOP and ASTRAL data and classification of new structures. Nucleic Acids Res 42:D304–D309

    Article  CAS  Google Scholar 

  4. http://scop.berkeley.edu/

  5. Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, Potter SC, Punta M, Qureshi M, Sangrador-Vegas A, Salazar GA, Tate J, Bateman A (2016) The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res 44(Database Issue):D279–D285

    Article  CAS  Google Scholar 

  6. https://pfam.xfam.org/

  7. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242

    Article  CAS  Google Scholar 

  8. www.rcsb.org

  9. Sternberg MJE (1996) Protein structure prediction—principles and approaches. In: Sternebrg MJE (ed) Protein structure prediction: a practical approach. IRL Press, Oxford

    Google Scholar 

  10. Roterman I, Banach M, Kalinowska B, Konieczny L (2016) Influence of the aqueous environment on protein structure—a plausible hypothesis concerning the mechanism of amyloidogenesis. Entropy 18(10):351

    Article  Google Scholar 

  11. Roterman I, Banach M, Konieczny L (2017) Application of the fuzzy oil drop model describes amyloid as a ribbonlike micelle. Entropy 19(4):167

    Article  Google Scholar 

  12. Kalinowska B, Banach M, Konieczny L, Roterman I (2015) Application of divergence entropy to characterize the structure of the hydrophobic core in DNA interacting proteins. Entropy 17(3):1477–1507

    Article  CAS  Google Scholar 

  13. Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132

    Article  CAS  Google Scholar 

  14. Konieczny L, Brylinski M, Roterman I (2006) Gauss function based model of hydrophobicity density in proteins. In Silico Biol 6:15–22

    CAS  PubMed  Google Scholar 

  15. Kauzmann W (1959) Some factors in the interpretation of protein denaturation. Adv Protein Chem 14:1–63

    Article  CAS  Google Scholar 

  16. Levitt M (1976) A simplified representation of protein conformations for rapid simulation of protein folding. J Mol Biol 104:59–107

    Article  CAS  Google Scholar 

  17. Kullback S, Leibler RA (1951) On information and sufficiency. Ann Math Stat 22:79–86

    Article  Google Scholar 

  18. Dygut J, Kalinowska B, Banach M, Piwowar M, Konieczny L, Roterman I (2016) Structural interface forms and their involvement in stabilization of multidomain proteins or protein complexes. Int J Mol Sci 17(10):E1741

    Article  Google Scholar 

  19. Kalinowska B, Banach M, Wiśniowski Z, Konieczny L, Roterman I (2017) Is the hydrophobic core a universal structural element in proteins? J Mol Model 23(7):205

    Article  Google Scholar 

  20. Devlin TM (2011) Textbook of biochemistry with clinical correlations, vol 7. Wiley, New York

    Google Scholar 

  21. Han KD, Park SJ, Jang SB, Lee BJ (2008) Solution structure of conserved hypothetical protein HP0892 from Helicobacter pylori. Proteins 70(2):599–602

    Article  CAS  Google Scholar 

  22. Banach M, Konieczny L, Roterman I (2014) The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function. J Theor Biol 359:6–17

    Article  CAS  Google Scholar 

  23. Fokkens J, Klebe G (2006) A simple protocol to estimate differences in protein binding affinity for enantiomers without prior resolution of racemates. Angew Chem Int Ed Engl 45(6):985–989

    Article  CAS  Google Scholar 

  24. Jones EY, Davis SJ, Williams AF, Harlos K, Stuart DI (1992) Crystal structure at 2.8 A resolution of a soluble form of the cell adhesion molecule CD2. Nature 360(6401):232–239

    Article  CAS  Google Scholar 

  25. Kister A (2015) Amino acid distribution rules predict protein fold: protein grammar for beta-strand sandwich-like structures. Biomolecules 5:41–59

    Article  CAS  Google Scholar 

  26. Fokas AS, Papatheodorou TS, Kister AE, Gelfand IM (2005) A geometric construction determines all permissible strand arrangements of sandwich proteins. PNAS 102(44):15851–15853

    Article  CAS  Google Scholar 

  27. Fokas AS, Gelfand IM, Kister AE (2004) Prediction of the structural motifs of sandwich proteins. PNAS 101(48):16780–16783

    Article  CAS  Google Scholar 

  28. McManus AM, Nielsen KJ, Marcus JP, Harrison SJ, Green JL, Manners JM, Craik DJ (1999) MiAMP1, a novel protein from Macadamia integrifolia adopts a Greek key beta-barrel fold unique amongst plant antimicrobial proteins. J Mol Biol 293(3):629–638

    Article  CAS  Google Scholar 

  29. Banach M, Kalinowska B, Konieczny L, Roterman I (2016) Role of disulfide bonds in stabilizing the conformation of selected enzymes—an approach based on divergence entropy applied to the structure of hydrophobic core in proteins. Entropy 18(3):67

    Article  Google Scholar 

  30. Fu Z, Wang M, Paschke R, Rao KS, Frerman FE, Kim JJ (2004) The crystal structure and mechanism of human glutaryl-CoA dehydrogenase. Biochemistry 43:9674–9684

    Article  CAS  Google Scholar 

  31. Banach M, Prudhomme N, Carpentier M, Duprat E, Papandreou N, Kalinowska B, Chomilier J, Roterman I (2015) Contribution to the prediction of the fold code: application to immunoglobulin and flavodoxin cases. PLoS One 10(4):e0125098

    Article  Google Scholar 

  32. Li W, Kinch LN, Karplus PA, Grishin NV (2015) ChSeq: a database of chameleon sequences. Protein Sci 24(7):1075–1086. https://doi.org/10.1002/pro.2689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kalinowska B, Banach M, Konieczny L, Roterman I (2016) Chameleon sequences—sequence-to-structure relation in proteins. J Proteomics Bioinform 9:264–275

    Google Scholar 

  34. Gallego F, Sol D, Chornet JJC, Cavada BS. PDB

    Google Scholar 

  35. Doki S, Kato HE, Solcan N, Iwaki M, Koyama M, Hattori M, Iwase N, Tsukazaki T, Sugita Y, Kandori H, Newstead S, Ishitani R, Nureki O (2013) Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT. Proc Natl Acad Sci U S A 110(28):11343–11348

    Article  CAS  Google Scholar 

  36. Binkowski TA, Xu X, Edwards A, Savchenko A, Joachimiak A. Midwest Center for Structural Genomics (MCSG)—PDB

    Google Scholar 

  37. Joint Center for Structural Genomics (JCSG)—PDB

    Google Scholar 

  38. Krieg S, Huché F, Diederichs K, Izadi-Pruneyre N, Lecroisey A, Wandersman C, Delepelaire P, Welte W (2009) Heme uptake across the outer membrane as revealed by crystal structures of the receptor-hemophore complex. Proc Natl Acad Sci U S A 106(4):1045–1050

    Article  CAS  Google Scholar 

  39. Gopal B, Haire LF, Cox RA, Jo Colston M, Major S, Brannigan JA, Smerdon SJ, Dodson G (2000) The crystal structure of NusB from Mycobacterium tuberculosis. Nat Struct Biol 7(6):475–478

    Article  CAS  Google Scholar 

  40. Williams GJ, Breazeale SD, Raetz CR, Naismith JH (2005) Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesis. J Biol Chem 280(24):23000–23008

    Article  CAS  Google Scholar 

  41. Malashkevich VN, Xiang DF, Raushel FM, Almo SC, Burley SK. New York Sgx Research Center For Structural Genomics (Nysgxrc)—PDB

    Google Scholar 

  42. Benarroch D, Smith P, Shuman S (2008) Characterization of a trifunctional mimivirus mRNA capping enzyme and crystal structure of the RNA triphosphatase domain. Structure 16(4):501–512

    Article  CAS  Google Scholar 

  43. Khan MB, Sponder G, Sjöblom B, Svidová S, Schweyen RJ, Carugo O, Djinović-Carugo K (2013) Structural and functional characterization of the N-terminal domain of the yeast Mg2+ channel Mrs2. Acta Crystallogr D Biol Crystallogr 69(Pt 9):1653–1664

    Article  CAS  Google Scholar 

  44. Holyoak T, Zhang B, Deng J, Tang Q, Prasannan CB, Fenton AW (2013) Energetic coupling between an oxidizable cysteine and the phosphorylatable N-terminus of human liver pyruvate kinase. Biochemistry 52(3):466–476

    Article  CAS  Google Scholar 

  45. Leonetti MD, Yuan P, Hsiung Y, Mackinnon R (2012) Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel. Proc Natl Acad Sci U S A 109(47):19274–19279

    Article  CAS  Google Scholar 

  46. Joint Center for Structural Genomics (JCSG). Crystal structure of ftsz-like protein of unknown function (zp_00109722.1) from nostoc punctiforme pcc 73102 at 1.22 a resolution—PDB

    Google Scholar 

  47. Nishino T, Komori K, Ishino Y, Morikawa K (2003) X-ray and biochemical anatomy of an archaeal XPF/Rad1/Mus81 family nuclease: similarity between its endonuclease domain and restriction enzymes. Structure 11(4):445–457

    Article  CAS  Google Scholar 

  48. Ebihara A, Okamoto A, Kousumi Y, Yamamoto H, Masui R, Ueyama N, Yokoyama S, Kuramitsu S (2005) Structure-based functional identification of a novel heme-binding protein from Thermus thermophilus HB8. J Struct Funct Genom 6(1):21–32

    Article  CAS  Google Scholar 

  49. Altun M, Walter TS, Kramer HB, Herr P, Iphöfer A, Boström J, David Y, Komsany A, Ternette N, Navon A, Stuart DI, Ren J, Kessler BM (2015) The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. PLoS One 10(1):e0115344

    Article  Google Scholar 

  50. Irving JA, Cabrita LD, Rossjohn J, Pike RN, Bottomley SP, Whisstock JC (2003) The 1.5 A crystal structure of a prokaryote serpin: controlling conformational change in a heated environment. Structure 11(4):387–397

    Article  CAS  Google Scholar 

  51. Mancusso R, Gregorio GG, Liu Q, Wang DN (2012) Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter. Nature 491(7425):622–626

    Article  CAS  Google Scholar 

  52. Ferguson AD, Welte W, Hofmann E, Lindner B, Holst O, Coulton JW, Diederichs K (2000) A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins. Structure 8(6):585–592

    Article  CAS  Google Scholar 

  53. Nagano S, Cupp-Vickery JR, Poulos TL (2005) Crystal structures of the ferrous dioxygen complex of wild-type cytochrome P450eryF and its mutants, A245S and A245T: investigation of the proton transfer system in P450eryF. J Biol Chem 280(23):22102–22107

    Article  CAS  Google Scholar 

  54. Craig TK, Abendroth J, Lorimer D, Burgin AB Jr, Segall A, Rohwer F. Crystal structure of a pentameric capsid protein isol from metagenomic phage sequences solved by iodide sad phasing—PDB

    Google Scholar 

  55. Iverson TM, Alber BE, Kisker C, Ferry JG, Rees DC (2000) A closer look at the active site of gamma-class carbonic anhydrases: high-resolution crystallographic studies of the carbonic anhydrase from Methanosarcina thermophila. Biochemistry 39(31):9222–9231

    Article  CAS  Google Scholar 

  56. Roterman I, Banach M, Konieczny L (2017) Propagation of fibrillar structural forms in proteins stopped by naturally occurring short polypeptide chain fragments. Pharmaceuticals (Basel) 10(4):89

    Article  Google Scholar 

  57. Roterman I, Banach M, Konieczny L (2018) Towards the design of anti-amyloid short peptide helices. Bioinformation 14(1):1–7

    Article  Google Scholar 

  58. Xiao Y, Ma B, McElheny D, Parthasarathy S, Long F, Hoshi M, Nussinov R, Ishii Y (2015) A beta (1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease. Nat Struct Mol Biol 22:499–505

    Article  CAS  Google Scholar 

  59. Chiti F, Dobson CM (2017) Protein misfolding, amyloid formation and human disease; a summary of progress over the last decade. Annu Rev Biochem 86:27–68

    Article  CAS  Google Scholar 

  60. Gremer L, Schölzel D, Schenk C, Reinartz E, Labahn J, Ravelli RBG, Tusche M, Lopez-Iglesias C, Hoyer W, Heise H, Willbold D, Schröder GF (2017) Fibril structure of amyloid-β(1–42) by cryo-electron microscopy. Science 358(6359):116–119

    Article  CAS  Google Scholar 

  61. Biedermann F, Nau WM, Schneider H-J (2014) The hydrophobic effect revisited—studies with supramolecular complexes imply high-energy water as a noncovalent driving force. Angew Chem 53:11158–11171

    Article  CAS  Google Scholar 

  62. Schutzius TM, Jung S, Maitra T, Graeber G, Köhme M, Poulikakos D (2015) Spontaneous droplet trampolining on rigid superhydrophobic surfaces. Nature 527(7576):82–85

    Article  CAS  Google Scholar 

  63. Kim KH, Späh A, Pathak H, Perakis F, Mariedahl D, Amann-Winkel K, Sellberg JA, Lee JH, Kim S, Park J, Nam KH, Katayama T, Nilsson A (2017) Maxima in the thermodynamic response and correlation functions of deeply supercooled water. Science 358(6370):1589–1593

    Article  CAS  Google Scholar 

  64. Konieczny L, Roterman I (2012) Conclusions. In: Roterman-Konieczna I (ed) Protein folding in silico. Elsevier, Oxford, pp 191–203

    Chapter  Google Scholar 

  65. Anfinsen CB (1973) Principles that govern the folding of protein chains. Science 181:223–230

    Article  CAS  Google Scholar 

  66. Kim W, Xiao J, Chaikof EL (2011) Recombinant amphiphilic protein micelles for drug delivery. Langmuir 27(23):14329–14334

    Article  CAS  Google Scholar 

  67. Kim W, Brady C, Chaikof EL (2012) Amphiphilic protein micelles for targeted in vivo imaging. Acta Biomater 8(7):2476–2482

    Article  CAS  Google Scholar 

  68. Schott H (1968) On the similarity between micelles of nonionic detergents and globular proteins. J Am Oil Chem Soc 45(11):823–824

    Article  CAS  Google Scholar 

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Acknowledgments

The authors are indebted to Piotr Nowakowski and Anna Śmietańska for their editorial and technical help. This research was supported by Jagiellonian University Medical College grant no. K/ZDS/006363.

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Authors and Affiliations

  1. Department of Bioinformatics and Telemedicine, Jagiellonian University, Medical College, Kraków, Poland

    Mateusz Banach & Irena Roterman

  2. Chair of Medical Biochemistry, Jagiellonian University, Medical College, Kraków, Poland

    Leszek Konieczny

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  1. Mateusz Banach
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  2. Leszek Konieczny
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  3. Irena Roterman
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Correspondence to Irena Roterman .

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Editors and Affiliations

  1. Department of Mathematics, Rutgers University, Piscataway, NJ, USA

    Alexander E. Kister

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Banach, M., Konieczny, L., Roterman, I. (2019). Secondary and Supersecondary Structure of Proteins in Light of the Structure of Hydrophobic Cores. In: Kister, A. (eds) Protein Supersecondary Structures. Methods in Molecular Biology, vol 1958. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9161-7_19

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  • DOI: https://doi.org/10.1007/978-1-4939-9161-7_19

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  • Publisher Name: Humana Press, New York, NY

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