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A logical OR redundancy within the Asx-Pro-Asx-Gly type I beta-turn motif.

Lee J, Dubey VK, Longo LM, Blaber M
J Mol Biol 377 1251-64 (2008)
Related entries: 3b9u, 3ba4, 3ba5, 3ba7, 3bad, 3bag, 3bao, 3baq, 3bau, 3bav, 3bb2

Cited: 17 times
EuropePMC logo PMID: 18308335

Abstract

Turn secondary structure is essential to the formation of globular protein architecture. Turn structures are, however, much more complex than either alpha-helix or beta-sheet, and the thermodynamics and folding kinetics are poorly understood. Type I beta-turns are the most common type of reverse turn, and they exhibit a statistical consensus sequence of Asx-Pro-Asx-Gly (where Asx is Asp or Asn). A comprehensive series of individual and combined Asx mutations has been constructed within three separate type I 3:5 G1 bulge beta-turns in human fibroblast growth factor-1, and their effects on structure, stability, and folding have been determined. The results show a fundamental logical OR relationship between the Asx residues in the motif, involving H-bond interactions with main-chain amides within the turn. These interactions can be modulated by additional interactions with residues adjacent to the turn at positions i+4 and i+6. The results show that the Asx residues in the turn motif make a substantial contribution to the overall stability of the protein, and the Asx logical OR relationship defines a redundant system that can compensate for deleterious point mutations. The results also show that the stability of the turn is unlikely to be the prime determinant of formation of turn structure in the folding transition state.

Reviews citing this publication (3)

  1. Protein design at the interface of the pre-biotic and biotic worlds. Longo LM, Blaber M. Arch Biochem Biophys 526 16-21 (2012)
  2. Protein comparability assessments and potential applicability of high throughput biophysical methods and data visualization tools to compare physical stability profiles. Alsenaidy MA, Jain NK, Kim JH, Middaugh CR, Volkin DB. Front Pharmacol 5 39 (2014)
  3. Structural determinants of protein folding. Kang TS, Kini RM. Cell Mol Life Sci 66 2341-2361 (2009)

Articles citing this publication (14)

  1. Experimental support for the evolution of symmetric protein architecture from a simple peptide motif. Lee J, Blaber M. Proc Natl Acad Sci U S A 108 126-130 (2011)
  2. Increasing protein stability by improving beta-turns. Fu H, Grimsley GR, Razvi A, Scholtz JM, Pace CN. Proteins 77 491-498 (2009)
  3. Simplified protein design biased for prebiotic amino acids yields a foldable, halophilic protein. Longo LM, Lee J, Blaber M. Proc Natl Acad Sci U S A 110 2135-2139 (2013)
  4. A polypeptide "building block" for the β-trefoil fold identified by "top-down symmetric deconstruction". Lee J, Blaber SI, Dubey VK, Blaber M. J Mol Biol 407 744-763 (2011)
  5. Distant Phe345 mutation compromises the stability and activity of Mycobacterium tuberculosis isocitrate lyase by modulating its structural flexibility. Shukla H, Shukla R, Sonkar A, Pandey T, Tripathi T. Sci Rep 7 1058 (2017)
  6. Experimental support for the foldability-function tradeoff hypothesis: segregation of the folding nucleus and functional regions in fibroblast growth factor-1. Longo L, Lee J, Blaber M. Protein Sci 21 1911-1920 (2012)
  7. An empirical phase diagram approach to investigate conformational stability of "second-generation" functional mutants of acidic fibroblast growth factor-1. Alsenaidy MA, Wang T, Kim JH, Joshi SB, Lee J, Blaber M, Volkin DB, Middaugh CR. Protein Sci 21 418-432 (2012)
  8. Structural basis of conserved cysteine in the fibroblast growth factor family: evidence for a vestigial half-cystine. Lee J, Blaber M. J Mol Biol 393 128-139 (2009)
  9. Design, synthesis and evaluation of antimicrobial activity of N-terminal modified Leucocin A analogues. Bodapati KC, Soudy R, Etayash H, Stiles M, Kaur K. Bioorg Med Chem 21 3715-3722 (2013)
  10. Elimination of a cis-proline-containing loop and turn optimization stabilizes a protein and accelerates its folding. Jakob RP, Zierer BK, Weininger U, Hofmann SD, Lorenz SH, Balbach J, Dobbek H, Schmid FX. J Mol Biol 399 331-346 (2010)
  11. Identification of high affinity and low molecular alternatives of boceprevir against SARS-CoV-2 main protease: A virtual screening approach. Borkotoky S, Banerjee M, Modi GP, Dubey VK. Chem Phys Lett 770 138446 (2021)
  12. Intramolecular C---H···O hydrogen-bond mediated stabilization of a cis-DPro imide-bond in a stereocontrolled heterochiral model peptide. Bhadbhade MM, Kishore R. Biopolymers 97 73-82 (2012)
  13. On the turn-inducing properties of asparagine: the structuring role of the amide side chain, from isolated model peptides to crystallized proteins. Habka S, Sohn WY, Vaquero-Vara V, Géléoc M, Tardivel B, Brenner V, Gloaguen E, Mons M. Phys Chem Chem Phys 20 3411-3423 (2018)
  14. Vitamin C and Vitamin D3 show strong binding with the amyloidogenic region of G555F mutant of Fibrinogen A alpha-chain associated with renal amyloidosis: proposed possible therapeutic intervention. Pande M, Kundu D, Srivastava R. Mol Divers 26 939-949 (2022)


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