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. 1995 Aug;4(8):1446–1456. doi: 10.1002/pro.5560040802

Structural analysis of the N- and C-termini in a peptide with consensus sequence.

Y Gong 1, H X Zhou 1, M Guo 1, N R Kallenbach 1
PMCID: PMC2143179  PMID: 8520470

Abstract

We present a structural analysis of a peptide, the sequence of which includes amino acids that show preferences for specific positions near the N- and C-termini in protein helices. This peptide has the sequence ac-YMSEDELKAAEAAFKRHGVP-amide, which includes a strong version of an N-terminal Harper-Rose capping box structure as well as a Gly located close to the C-terminus designed to elucidate its role in C-terminal capping. The sequence of five residues at the middle is inserted to separate effects at the two ends via a helix-stabilizing linker. Application of a simulated annealing procedure using interproton distance constraints derived from 1H NOESY experiments in water reveals the presence of a C-terminal structure in this model. The C-terminus forms a folded back structure in a significant fraction of structures generated by the annealing, in most of which Gly assumes an alpha L conformation. This structure occurs within a highly flexible region of the molecule and hence is occupied only a fraction of the time.

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Selected References

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  1. Bork P., Preissner R. On alpha-helices terminated by glycine. 2. Recognition by sequence patterns. Biochem Biophys Res Commun. 1991 Oct 31;180(2):666–672. doi: 10.1016/s0006-291x(05)81117-9. [DOI] [PubMed] [Google Scholar]
  2. Brandts J. F., Kaplan L. J. Derivative sspectroscopy applied to tyrosyl chromophores. Studies on ribonuclease, lima bean inhibitors, insulin, and pancreatic trypsin inhibitor. Biochemistry. 1973 May 8;12(10):2011–2024. doi: 10.1021/bi00734a027. [DOI] [PubMed] [Google Scholar]
  3. Bruch M. D., Dhingra M. M., Gierasch L. M. Side chain-backbone hydrogen bonding contributes to helix stability in peptides derived from an alpha-helical region of carboxypeptidase A. Proteins. 1991;10(2):130–139. doi: 10.1002/prot.340100206. [DOI] [PubMed] [Google Scholar]
  4. Creamer T. P., Rose G. D. Side-chain entropy opposes alpha-helix formation but rationalizes experimentally determined helix-forming propensities. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5937–5941. doi: 10.1073/pnas.89.13.5937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dauber-Osguthorpe P., Roberts V. A., Osguthorpe D. J., Wolff J., Genest M., Hagler A. T. Structure and energetics of ligand binding to proteins: Escherichia coli dihydrofolate reductase-trimethoprim, a drug-receptor system. Proteins. 1988;4(1):31–47. doi: 10.1002/prot.340040106. [DOI] [PubMed] [Google Scholar]
  6. Doig A. J., Chakrabartty A., Klingler T. M., Baldwin R. L. Determination of free energies of N-capping in alpha-helices by modification of the Lifson-Roig helix-coil therapy to include N- and C-capping. Biochemistry. 1994 Mar 22;33(11):3396–3403. doi: 10.1021/bi00177a033. [DOI] [PubMed] [Google Scholar]
  7. Forood B., Feliciano E. J., Nambiar K. P. Stabilization of alpha-helical structures in short peptides via end capping. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):838–842. doi: 10.1073/pnas.90.3.838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gans P. J., Lyu P. C., Manning M. C., Woody R. W., Kallenbach N. R. The helix-coil transition in heterogeneous peptides with specific side-chain interactions: theory and comparison with CD spectral data. Biopolymers. 1991 Nov;31(13):1605–1614. doi: 10.1002/bip.360311315. [DOI] [PubMed] [Google Scholar]
  9. Gippert G. P., Yip P. F., Wright P. E., Case D. A. Computational methods for determining protein structures from NMR data. Biochem Pharmacol. 1990 Jul 1;40(1):15–22. doi: 10.1016/0006-2952(90)90172-h. [DOI] [PubMed] [Google Scholar]
  10. Hagler A. T., Moult J. Computer simulation of the solvent structure around biological macromolecules. Nature. 1978 Mar 16;272(5650):222–226. doi: 10.1038/272222a0. [DOI] [PubMed] [Google Scholar]
  11. Harper E. T., Rose G. D. Helix stop signals in proteins and peptides: the capping box. Biochemistry. 1993 Aug 3;32(30):7605–7609. doi: 10.1021/bi00081a001. [DOI] [PubMed] [Google Scholar]
  12. Kumar A., Ernst R. R., Wüthrich K. A two-dimensional nuclear Overhauser enhancement (2D NOE) experiment for the elucidation of complete proton-proton cross-relaxation networks in biological macromolecules. Biochem Biophys Res Commun. 1980 Jul 16;95(1):1–6. doi: 10.1016/0006-291x(80)90695-6. [DOI] [PubMed] [Google Scholar]
  13. Levitt M. Conformational preferences of amino acids in globular proteins. Biochemistry. 1978 Oct 3;17(20):4277–4285. doi: 10.1021/bi00613a026. [DOI] [PubMed] [Google Scholar]
  14. Lyu P. C., Liff M. I., Marky L. A., Kallenbach N. R. Side chain contributions to the stability of alpha-helical structure in peptides. Science. 1990 Nov 2;250(4981):669–673. doi: 10.1126/science.2237416. [DOI] [PubMed] [Google Scholar]
  15. Lyu P. C., Wemmer D. E., Zhou H. X., Pinker R. J., Kallenbach N. R. Capping interactions in isolated alpha helices: position-dependent substitution effects and structure of a serine-capped peptide helix. Biochemistry. 1993 Jan 19;32(2):421–425. doi: 10.1021/bi00053a006. [DOI] [PubMed] [Google Scholar]
  16. Maple J. R., Dinur U., Hagler A. T. Derivation of force fields for molecular mechanics and dynamics from ab initio energy surfaces. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5350–5354. doi: 10.1073/pnas.85.15.5350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Merutka G., Lipton W., Shalongo W., Park S. H., Stellwagen E. Effect of central-residue replacements on the helical stability of a monomeric peptide. Biochemistry. 1990 Aug 14;29(32):7511–7515. doi: 10.1021/bi00484a021. [DOI] [PubMed] [Google Scholar]
  18. PAULING L., COREY R. B., BRANSON H. R. The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A. 1951 Apr;37(4):205–211. doi: 10.1073/pnas.37.4.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rance M., Sørensen O. W., Bodenhausen G., Wagner G., Ernst R. R., Wüthrich K. Improved spectral resolution in cosy 1H NMR spectra of proteins via double quantum filtering. Biochem Biophys Res Commun. 1983 Dec 16;117(2):479–485. doi: 10.1016/0006-291x(83)91225-1. [DOI] [PubMed] [Google Scholar]
  20. Richardson J. S., Richardson D. C. Amino acid preferences for specific locations at the ends of alpha helices. Science. 1988 Jun 17;240(4859):1648–1652. doi: 10.1126/science.3381086. [DOI] [PubMed] [Google Scholar]
  21. Seale J. W., Srinivasan R., Rose G. D. Sequence determinants of the capping box, a stabilizing motif at the N-termini of alpha-helices. Protein Sci. 1994 Oct;3(10):1741–1745. doi: 10.1002/pro.5560031014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Serrano L., Fersht A. R. Capping and alpha-helix stability. Nature. 1989 Nov 16;342(6247):296–299. doi: 10.1038/342296a0. [DOI] [PubMed] [Google Scholar]

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