Advertisement

βαβ Super-Secondary Motifs: Sequence, Structural Overview, and Pursuit of Potential Autonomously Folding βαβ Sequences from (β/α)8/TIM Barrels

  • Rajasekhar Varma Kadamuri
  • Shivkumar Sharma Irukuvajjula
  • Ramakrishna VadrevuEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1958)

Abstract

βαβ super-secondary structures constitute the basic building blocks of (β/α)8 class of proteins. Despite the success in designing super-secondary structures, till date, there is not a single example of a natural βαβ sequence known to fold in isolation. In this chapter, to address the finding the “needles” in the haystack scenario, we have combined the sequence preferences and structural features of independent βαβ motifs, dictated by natural selection, with rationally derived parameters from a designed βαβ motif adopting stable fold in solution. Guided by this approach, a set of potential βαβ sequences from (β/α)8/TIM barrels are proposed as likely candidates for autonomously folding based on the assessment of their foldability.

Key words

βαβ motifs Super-secondary structures Main-chain to side-chain hydrogen bonding (β/α)8 barrels TIM barrel 

Notes

Acknowledgments

The authors thank University Grants Commission, India, for the initial part of this research. RVK is grateful to UGC, India, and Birla Institute of Technology and Science Pilani, Hyderabad Campus, for financial support in the form of research fellowship.

References

  1. 1.
    Grishin NV (2001) Fold change in evolution of protein structures. J Struct Biol 134(2–3):167–185.  https://doi.org/10.1006/jsbi.2001.4335CrossRefPubMedGoogle Scholar
  2. 2.
    Soding J, Lupas AN (2003) More than the sum of their parts: on the evolution of proteins from peptides. Bio Essays 25(9):837–846.  https://doi.org/10.1002/bies.10321CrossRefGoogle Scholar
  3. 3.
    Salem GM, Hutchinson EG, Orengo CA, Thornton JM (1999) Correlation of observed fold frequency with the occurrence of local structural motifs. J Mol Biol 287(5):969–981.  https://doi.org/10.1006/jmbi.1999.2642CrossRefPubMedGoogle Scholar
  4. 4.
    Cui Y, Wong WH, Bornberg-Bauer E, Chan HS (2002) Recombinatoric exploration of novel folded structures: a heteropolymer-based model of protein evolutionary landscapes. Proc Natl Acad Sci U S A 99(2):809–814.  https://doi.org/10.1073/pnas.022240299CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bogarad LD, Deem MW (1999) A hierarchical approach to protein molecular evolution. Proc Natl Acad Sci U S A 96(6):2591–2595CrossRefGoogle Scholar
  6. 6.
    Marcotte EM, Pellegrini M, Yeates TO, Eisenberg D (1999) A census of protein repeats. J Mol Biol 293(1):151–160.  https://doi.org/10.1006/jmbi.1999.3136CrossRefPubMedGoogle Scholar
  7. 7.
    Doolittle RF (1995) The multiplicity of domains in proteins. Annu Rev Biochem 64:287–314.  https://doi.org/10.1146/annurev.bi.64.070195.001443CrossRefPubMedGoogle Scholar
  8. 8.
    Lupas AN, Ponting CP, Russell RB (2001) On the evolution of protein folds: are similar motifs in different protein folds the result of convergence, insertion, or relics of an ancient peptide world? J Struct Biol 134(2–3):191–203.  https://doi.org/10.1006/jsbi.2001.4393CrossRefPubMedGoogle Scholar
  9. 9.
    Orengo CA, Thornton JM (2005) Protein families and their evolution-a structural perspective. Annu Rev Biochem 74:867–900.  https://doi.org/10.1146/annurev.biochem.74.082803.133029CrossRefPubMedGoogle Scholar
  10. 10.
    Soding J, Biegert A, Lupas AN (2005) The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res 33(Web Server):W244–W248.  https://doi.org/10.1093/nar/gki408CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Riechmann L, Winter G (2000) Novel folded protein domains generated by combinatorial shuffling of polypeptide segments. Proc Natl Acad Sci U S A 97(18):10068–10073.  https://doi.org/10.1073/pnas.170145497CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Riechmann L, Winter G (2006) Early protein evolution: building domains from ligand-binding polypeptide segments. J Mol Biol 363(2):460–468.  https://doi.org/10.1016/j.jmb.2006.08.031CrossRefPubMedGoogle Scholar
  13. 13.
    Panchenko AR, Luthey-Schulten Z, Cole R, Wolynes PG (1997) The foldon universe: a survey of structural similarity and self-recognition of independently folding units. J Mol Biol 272(1):95–105.  https://doi.org/10.1006/jmbi.1997.1205CrossRefPubMedGoogle Scholar
  14. 14.
    Berezovsky IN, Guarnera E, Zheng Z (2017) Basic units of protein structure, folding, and function. Prog Biophys Mol Biol 128:85–99.  https://doi.org/10.1016/j.pbiomolbio.2016.09.009CrossRefPubMedGoogle Scholar
  15. 15.
    Zeng J, Jiang F, Wu YD (2016) Folding simulations of an alpha-helical hairpin motif alphatalpha with residue-specific force fields. J Phys Chem B 120(1):33–41.  https://doi.org/10.1021/acs.jpcb.5b09027CrossRefPubMedGoogle Scholar
  16. 16.
    Blanco FJ, Rivas G, Serrano L (1994) A short linear peptide that folds into a native stable beta-hairpin in aqueous solution. Nat Struct Biol 1(9):584–590CrossRefGoogle Scholar
  17. 17.
    Searle MS, Williams DH, Packman LC (1995) A short linear peptide derived from the N-terminal sequence of ubiquitin folds into a water-stable non-native beta-hairpin. Nat Struct Biol 2(11):999–1006CrossRefGoogle Scholar
  18. 18.
    Stanger HE, Syud FA, Espinosa JF, Giriat I, Muir T, Gellman SH (2001) Length-dependent stability and strand length limits in antiparallel beta-sheet secondary structure. Proc Natl Acad Sci U S A 98(21):12015–12020.  https://doi.org/10.1073/pnas.211536998CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Cochran AG, Skelton NJ, Starovasnik MA (2001) Tryptophan zippers: stable, monomeric beta-hairpins. Proc Natl Acad Sci U S A 98(10):5578–5583.  https://doi.org/10.1073/pnas.091100898CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Sadqi M, de Alba E, Perez-Jimenez R, Sanchez-Ruiz JM, Munoz V (2009) A designed protein as experimental model of primordial folding. Proc Natl Acad Sci U S A 106(11):4127–4132.  https://doi.org/10.1073/pnas.0812108106CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Religa TL, Johnson CM, Vu DM, Brewer SH, Dyer RB, Fersht AR (2007) The helix-turn-helix motif as an ultrafast independently folding domain: the pathway of folding of Engrailed homeodomain. Proc Natl Acad Sci U S A 104(22):9272–9277.  https://doi.org/10.1073/pnas.0703434104CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Liang H, Chen H, Fan K, Wei P, Guo X, Jin C, Zeng C, Tang C, Lai L (2009) De novo design of a beta alpha beta motif. Angew Chem 48(18):3301–3303.  https://doi.org/10.1002/anie.200805476CrossRefGoogle Scholar
  23. 23.
    Marqusee S, Robbins VH, Baldwin RL (1989) Unusually stable helix formation in short alanine-based peptides. Proc Natl Acad Sci U S A 86(14):5286–5290CrossRefGoogle Scholar
  24. 24.
    Ihalainen JA, Paoli B, Muff S, Backus EH, Bredenbeck J, Woolley GA, Caflisch A, Hamm P (2008) Alpha-Helix folding in the presence of structural constraints. Proc Natl Acad Sci U S A 105(28):9588–9593.  https://doi.org/10.1073/pnas.0712099105CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Petukhov M, Tatsu Y, Tamaki K, Murase S, Uekawa H, Yoshikawa S, Serrano L, Yumoto N (2009) Design of stable alpha-helices using global sequence optimization. J Pept Sci 15(5):359–365.  https://doi.org/10.1002/psc.1122CrossRefPubMedGoogle Scholar
  26. 26.
    Yakimov A, Rychkov G, Petukhov M (2014) De novo design of stable alpha-helices. Methods Mol Biol 1216:1–14.  https://doi.org/10.1007/978-1-4939-1486-9_1CrossRefPubMedGoogle Scholar
  27. 27.
    Ramakrishna V, Sasidhar YU (1997) A pentapeptide model for an early folding step in the refolding of staphylococcal nuclease: the role of its turn propensity. Biopolymers 41(2):181–191.  https://doi.org/10.1002/(SICI)1097-0282(199702)41:2<181::AID-BIP5>3.0.CO;2-PCrossRefPubMedGoogle Scholar
  28. 28.
    Baker EG, Bartlett GJ, Porter Goff KL, Woolfson DN (2017) Miniprotein design: past, present, and prospects. Acc Chem Res 50(9):2085–2092.  https://doi.org/10.1021/acs.accounts.7b00186CrossRefPubMedGoogle Scholar
  29. 29.
    Kister AE, Potapov V (2013) Amino acid distribution rules predict protein fold. Biochem Soc Trans 41(2):616–619.  https://doi.org/10.1042/BST20120308CrossRefPubMedGoogle Scholar
  30. 30.
    Struthers MD, Cheng RP, Imperiali B (1996) Design of a monomeric 23-residue polypeptide with defined tertiary structure. Science 271(5247):342–345CrossRefGoogle Scholar
  31. 31.
    Dahiyat BI, Mayo SL (1997) De novo protein design: fully automated sequence selection. Science 278(5335):82–87CrossRefGoogle Scholar
  32. 32.
    Nagano N, Orengo CA, Thornton JM (2002) One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions. J Mol Biol 321(5):741–765CrossRefGoogle Scholar
  33. 33.
    Yang X, Kathuria SV, Vadrevu R, Matthews CR (2009) Betaalpha-hairpin clamps brace betaalphabeta modules and can make substantive contributions to the stability of TIM barrel proteins. PLoS One 4(9):e7179.  https://doi.org/10.1371/journal.pone.0007179CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zitzewitz JA, Gualfetti PJ, Perkons IA, Wasta SA, Matthews CR (1999) Identifying the structural boundaries of independent folding domains in the alpha subunit of tryptophan synthase, a beta/alpha barrel protein. Protein Sci 8(6):1200–1209.  https://doi.org/10.1110/ps.8.6.1200CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Frenkel ZM, Trifonov EN (2005) Closed loops of TIM barrel protein fold. J Biomol Struct Dyn 22(6):643–656.  https://doi.org/10.1080/07391102.2005.10507032CrossRefPubMedGoogle Scholar
  36. 36.
    Huang PS, Feldmeier K, Parmeggiani F, Fernandez Velasco DA, Hocker B, Baker D (2016) De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. Nat Chem Biol 12(1):29–34.  https://doi.org/10.1038/nchembio.1966CrossRefPubMedGoogle Scholar
  37. 37.
    Koga N, Tatsumi-Koga R, Liu G, Xiao R, Acton TB, Montelione GT, Baker D (2012) Principles for designing ideal protein structures. Nature 491(7423):222–227.  https://doi.org/10.1038/nature11600CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Ochoa-Leyva A, Montero-Moran G, Saab-Rincon G, Brieba LG, Soberon X (2013) Alternative splice variants in TIM barrel proteins from human genome correlate with the structural and evolutionary modularity of this versatile protein fold. PLoS One 8(8):e70582.  https://doi.org/10.1371/journal.pone.0070582CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ochoa-Leyva A, Barona-Gomez F, Saab-Rincon G, Verdel-Aranda K, Sanchez F, Soberon X (2011) Exploring the structure-function loop adaptability of a (beta/alpha)(8)-barrel enzyme through loop swapping and hinge variability. J Mol Biol 411(1):143–157.  https://doi.org/10.1016/j.jmb.2011.05.027CrossRefPubMedGoogle Scholar
  40. 40.
    Ochoa-Leyva A, Soberon X, Sanchez F, Arguello M, Montero-Moran G, Saab-Rincon G (2009) Protein design through systematic catalytic loop exchange in the (beta/alpha)eight fold. J Mol Biol 387(4):949–964.  https://doi.org/10.1016/j.jmb.2009.02.022CrossRefPubMedGoogle Scholar
  41. 41.
    Nagarajan D, Deka G, Rao M (2015) Design of symmetric TIM barrel proteins from first principles. BMC Biochem 16:18.  https://doi.org/10.1186/s12858-015-0047-4CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Berezovsky IN, Grosberg AY, Trifonov EN (2000) Closed loops of nearly standard size: common basic element of protein structure. FEBS Lett 466(2–3):283–286CrossRefGoogle Scholar
  43. 43.
    Chintapalli SV, Yew BK, Illingworth CJ, Upton GJ, Reeves PJ, Parkes KE, Snell CR, Reynolds CA (2010) Closed loop folding units from structural alignments: experimental foldons revisited. J Comput Chem 31(15):2689–2701.  https://doi.org/10.1002/jcc.21562CrossRefPubMedGoogle Scholar
  44. 44.
    Kadumuri RV, Vadrevu R (2017) Diversity in alphabeta and betaalpha loop connections in TIM barrel proteins: implications for stability and design of the fold. Interdiscip Sci Comput Life Sci.  https://doi.org/10.1007/s12539-017-0250-7
  45. 45.
    Yang X, Vadrevu R, Wu Y, Matthews CR (2007) Long-range side-chain-main-chain interactions play crucial roles in stabilizing the (betaalpha)8 barrel motif of the alpha subunit of tryptophan synthase. Protein Sci 16(7):1398–1409.  https://doi.org/10.1110/ps.062704507CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Balasco N, Esposito L, De Simone A, Vitagliano L (2013) Role of loops connecting secondary structure elements in the stabilization of proteins isolated from thermophilic organisms. Protein Sci 22(7):1016–1023.  https://doi.org/10.1002/pro.2279CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Munoz V, Serrano L (1995) Elucidating the folding problem of helical peptides using empirical parameters. III. Temperature and pH dependence. J Mol Biol 245(3):297–308.  https://doi.org/10.1006/jmbi.1994.0024CrossRefPubMedGoogle Scholar
  48. 48.
    Munoz V, Serrano L (1995) Elucidating the folding problem of helical peptides using empirical parameters. II. Helix macrodipole effects and rational modification of the helical content of natural peptides. J Mol Biol 245(3):275–296CrossRefGoogle Scholar
  49. 49.
    Munoz V, Serrano L (1997) Development of the multiple sequence approximation within the AGADIR model of alpha-helix formation: comparison with Zimm-Bragg and Lifson-Roig formalisms. Biopolymers 41(5):495–509.  https://doi.org/10.1002/(SICI)1097-0282(19970415)41:5<495::AID-BIP2>3.0.CO;2-HCrossRefPubMedGoogle Scholar
  50. 50.
    Lacroix E, Viguera AR, Serrano L (1998) Elucidating the folding problem of alpha-helices: local motifs, long-range electrostatics, ionic-strength dependence and prediction of NMR parameters. J Mol Biol 284(1):173–191.  https://doi.org/10.1006/jmbi.1998.2145CrossRefPubMedGoogle Scholar
  51. 51.
    Streicher WW, Makhatadze GI (2006) Calorimetric evidence for a two-state unfolding of the beta-hairpin peptide trpzip4. J Am Chem Soc 128(1):30–31.  https://doi.org/10.1021/ja056392xCrossRefPubMedGoogle Scholar
  52. 52.
    Xu D, Zhang Y (2012) Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field. Proteins 80(7):1715–1735.  https://doi.org/10.1002/prot.24065CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Lamiable A, Thevenet P, Rey J, Vavrusa M, Derreumaux P, Tuffery P (2016) PEP-FOLD3: faster de novo structure prediction for linear peptides in solution and in complex. Nucleic Acids Res 44(W1):W449–W454.  https://doi.org/10.1093/nar/gkw329CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Shen Y, Maupetit J, Derreumaux P, Tuffery P (2014) Improved PEP-FOLD approach for peptide and miniprotein structure prediction. J Chem Theory Comput 10(10):4745–4758.  https://doi.org/10.1021/ct500592mCrossRefPubMedGoogle Scholar
  55. 55.
    Thevenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P, Tuffery P (2012) PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res 40. (Web Server issue:W288–W293.  https://doi.org/10.1093/nar/gks419CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Zhang Y, Skolnick J (2004) SPICKER: a clustering approach to identify near-native protein folds. J Comput Chem 25(6):865–871.  https://doi.org/10.1002/jcc.20011CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang Y, Skolnick J (2004) Scoring function for automated assessment of protein structure template quality. Proteins 57(4):702–710.  https://doi.org/10.1002/prot.20264CrossRefPubMedGoogle Scholar
  58. 58.
    Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17):3389–3402CrossRefGoogle Scholar
  59. 59.
    Sippl MJ (1990) Calculation of conformational ensembles from potentials of mean force. An approach to the knowledge-based prediction of local structures in globular proteins. J Mol Biol 213(4):859–883CrossRefGoogle Scholar
  60. 60.
    Schrodinger L (2015) The PyMOL Molecular Graphics System, Version 1.8Google Scholar
  61. 61.
    Crooks GE, Hon G, Chandonia JM, Brenner SE (2004) WebLogo: a sequence logo generator. Genome Res 14(6):1188–1190.  https://doi.org/10.1101/gr.849004CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Rajasekhar Varma Kadamuri
    • 1
  • Shivkumar Sharma Irukuvajjula
    • 1
  • Ramakrishna Vadrevu
    • 1
    Email author
  1. 1.Department of Biological SciencesBirla Institute of Technology and Science-PilaniHyderabadIndia

Personalised recommendations