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. 1988 May;85(10):3407–3411. doi: 10.1073/pnas.85.10.3407

Mechanochemical coupling in synthetic polypeptides by modulation of an inverse temperature transition.

D W Urry 1, B Haynes 1, H Zhang 1, R D Harris 1, K U Prasad 1
PMCID: PMC280220  PMID: 2897120

Abstract

For the polypentapeptide of elastin, (L-Val-L-Pro-Gly-L-Val-Gly)n, and appropriate analogs when suitably cross-linked, it has been previously demonstrated that development of elastomeric force at fixed length and length changes at fixed load occur as the result of an inverse temperature transition, with the temperature of the transition being inversely dependent on the hydrophobicity of the polypeptide. This suggests that at fixed temperature a chemical means of reversibly changing the hydrophobicity could be used for mechanochemical coupling. Evidence for this mechanism of mechanochemical coupling is given here with a 4%-Glu-polypentapeptide, in which the valine in position 4 is replaced in 1 out of 5 pentamers by a glutamic acid residue. Before cross-linking, the temperature for aggregation of 4%-Glu-polypentapeptide is remarkably sensitive to pH, shifting from 25 degrees C at pH 2 to 70 degrees C at pH 7.4 in phosphate-buffered saline (PBS). At 37 degrees C, the cross-linked 4%-Glu-polypentapeptide matrix in PBS undergoes a pH-modulated contraction and relaxation with a change from pH 4.3 to 3.3 and back. The mean distance between carboxylates at pH 4.3 in the elastomeric matrix is greater than 40 A, twice the mean distance between negatively charged species in PBS. Accordingly, charge-charge repulsion is expected to make little or no contribution to the coupling. Mechanochemical coupling is demonstrated at fixed load by monitoring pH dependence of length and at constant length by monitoring pH dependence of force. To our knowledge, this is the first demonstration of mechanochemical coupling in a synthetic polypeptide and the first system to provide a test of the recent proposal that chemical modulation of an inverse temperature transition can be a mechanism for mechanochemical coupling. It is suggested that phosphorylation and dephosphorylation may modulate structure and forces in proteins by locally shifting the temperatures of inverse temperature transitions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell J. R., Boohan R. C., Jones J. H., Moore R. M. A synthetic polypeptide related to elastin and its interaction with calcium ions. Int J Pept Protein Res. 1974;6(3):155–156. doi: 10.1111/j.1399-3011.1974.tb02373.x. [DOI] [PubMed] [Google Scholar]
  2. Bell J. R., Boohan R. C., Jones J. H., Moore R. M. Sequential polypeptides. Part IX. The synthesis of two sequential polypeptide elastin models. Int J Pept Protein Res. 1975;7(3):227–234. [PubMed] [Google Scholar]
  3. Eisenberg E., Hill T. L. Muscle contraction and free energy transduction in biological systems. Science. 1985 Mar 1;227(4690):999–1006. doi: 10.1126/science.3156404. [DOI] [PubMed] [Google Scholar]
  4. Hill T. L., Inesi G. Equilibrium cooperative binding of calcium and protons by sarcoplasmic reticulum ATPase. Proc Natl Acad Sci U S A. 1982 Jul;79(13):3978–3982. doi: 10.1073/pnas.79.13.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hill T. L., Kirschner M. W. Subunit treadmilling of microtubules or actin in the presence of cellular barriers: possible conversion of chemical free energy into mechanical work. Proc Natl Acad Sci U S A. 1982 Jan;79(2):490–494. doi: 10.1073/pnas.79.2.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hill T. L. Some general principles in free energy transduction. Proc Natl Acad Sci U S A. 1983 May;80(10):2922–2925. doi: 10.1073/pnas.80.10.2922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. KAUZMANN W. Some factors in the interpretation of protein denaturation. Adv Protein Chem. 1959;14:1–63. doi: 10.1016/s0065-3233(08)60608-7. [DOI] [PubMed] [Google Scholar]
  8. Prasad K. U., Iqbal M. A., Urry D. W. Utilization of 1-hydroxybenzotriazole in mixed anhydride coupling reactions. Int J Pept Protein Res. 1985 Apr;25(4):408–413. doi: 10.1111/j.1399-3011.1985.tb02193.x. [DOI] [PubMed] [Google Scholar]
  9. Sandberg L. B., Leslie J. G., Leach C. T., Alvarez V. L., Torres A. R., Smith D. W. Elastin covalent structure as determined by solid phase amino acid sequencing. Pathol Biol (Paris) 1985 Apr;33(4):266–274. [PubMed] [Google Scholar]
  10. Sandberg L. B., Soskel N. T., Leslie J. G. Elastin structure, biosynthesis, and relation to disease states. N Engl J Med. 1981 Mar 5;304(10):566–579. doi: 10.1056/NEJM198103053041004. [DOI] [PubMed] [Google Scholar]
  11. Thomas G. J., Jr, Prescott B., Urry D. W. Raman amide bands of type-II beta-turns in cyclo-(VPGVG)3 and poly-(VPGVG), and implications for protein secondary-structure analysis. Biopolymers. 1987 Jun;26(6):921–934. doi: 10.1002/bip.360260611. [DOI] [PubMed] [Google Scholar]
  12. Urry D. W. Entropic elastic processes in protein mechanisms. I. Elastic structure due to an inverse temperature transition and elasticity due to internal chain dynamics. J Protein Chem. 1988 Feb;7(1):1–34. doi: 10.1007/BF01025411. [DOI] [PubMed] [Google Scholar]
  13. Urry D. W. Entropic elastic processes in protein mechanisms. II. Simple (passive) and coupled (active) development of elastic forces. J Protein Chem. 1988 Apr;7(2):81–114. doi: 10.1007/BF01025240. [DOI] [PubMed] [Google Scholar]
  14. Urry D. W., Haynes B., Harris R. D. Temperature dependence of length of elastin and its polypentapeptide. Biochem Biophys Res Commun. 1986 Dec 15;141(2):749–755. doi: 10.1016/s0006-291x(86)80236-4. [DOI] [PubMed] [Google Scholar]
  15. Urry D. W., Khaled M. A., Rapaka R. S., Okamoto K. Nuclear Overhauser enhancement evidence for inverse temperature dependence of hydrophobic side chain proximity in the polytetrapeptide of tropoelastin. Biochem Biophys Res Commun. 1977 Dec 7;79(3):700–706. doi: 10.1016/0006-291x(77)91168-8. [DOI] [PubMed] [Google Scholar]
  16. Urry D. W., Long M. M., Cox B. A., Ohnishi T., Mitchell L. W., Jacobs M. The synthetic polypentapeptide of elastin coacervates and forms filamentous aggregates. Biochim Biophys Acta. 1974 Dec 18;371(2):597–602. doi: 10.1016/0005-2795(74)90057-9. [DOI] [PubMed] [Google Scholar]
  17. Urry D. W., Long M. M. On the conformation, coacervation and function of polymeric models of elastin. Adv Exp Med Biol. 1977;79:685–714. doi: 10.1007/978-1-4684-9093-0_59. [DOI] [PubMed] [Google Scholar]
  18. Urry D. W., Okamoto K., Harris R. D., Hendrix C. F., Long M. M. Synthetic, cross-linked polypentapeptide fo tropoelastin: an anisotropic, fibrillar elastomer. Biochemistry. 1976 Sep 7;15(18):4083–4089. doi: 10.1021/bi00663a026. [DOI] [PubMed] [Google Scholar]
  19. Urry D. W., Trapane T. L., Iqbal M., Venkatachalam C. M., Prasad K. U. Carbon-13 NMR relaxation studies demonstrate an inverse temperature transition in the elastin polypentapeptide. Biochemistry. 1985 Sep 10;24(19):5182–5189. doi: 10.1021/bi00340a034. [DOI] [PubMed] [Google Scholar]
  20. Urry D. W., Trapane T. L., McMichens R. B., Iqbal M., Harris R. D., Prasad K. U. Nitrogen-15 NMR relaxation study of inverse temperature transitions in elastin polypentapeptide and its cross-linked elastomer. Biopolymers. 1986;25 (Suppl):S209–S228. [PubMed] [Google Scholar]
  21. Urry D. W., Trapane T. L., Prasad K. U. Phase-structure transitions of the elastin polypentapeptide-water system within the framework of composition-temperature studies. Biopolymers. 1985 Dec;24(12):2345–2356. doi: 10.1002/bip.360241212. [DOI] [PubMed] [Google Scholar]
  22. Yeh H., Ornstein-Goldstein N., Indik Z., Sheppard P., Anderson N., Rosenbloom J. C., Cicila G., Yoon K., Rosenbloom J. Sequence variation of bovine elastin mRNA due to alternative splicing. Coll Relat Res. 1987 Sep;7(4):235–247. doi: 10.1016/s0174-173x(87)80030-4. [DOI] [PubMed] [Google Scholar]

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