Estimating the relative populations of 3(10)-helix and alpha-helix in Ala-rich peptides: A hydrogen exchange and high field NMR study

被引:110
作者
Millhauser, GL [1 ]
Stenland, CJ [1 ]
Hanson, P [1 ]
Bolin, KA [1 ]
vandeVen, FJM [1 ]
机构
[1] CATHOLIC UNIV NIJMEGEN,NIJMEGEN SON RES CTR,BIOPHYS CHEM LAB,NL-6525 ED NIJMEGEN,NETHERLANDS
关键词
nuclear magnetic resonance; helical peptide; alpha-helix; 3(10)-helix; conformational equilibria;
D O I
10.1006/jmbi.1997.0923
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent experimental and theoretical work suggests that alanine-rich peptides fold as a mixture of 3(10)-helix (i --> i + 3 hydrogen bonding) and alpha-helix (i --> i + 4 hydrogen bonding). In order to assess the relative proportions of the two conformers, NMR studies were performed on the 16 residue sequences: Ac-AAAAKAAAAKAAAAKA-NH2 (3K) and Ac-AMAAKAWAAKAAAARA-NH2 (MW). Hydrogen/deuterium-exchange kinetics measured for the first three amide protons of the 3K peptide indicate that the NH of Ala3 is partially protected from exchange. This result is consistent with the presence of an i --> i + 3 hydrogen bond between the carbonyl group of the acetyl blocking group and the NH group of Ala3. The MW peptide is a modified version of the 3K peptide, designed to increase alpha H signal dispersion. H-1 NMR spectra of the MW peptide at 750 MHz reveal a series of intermediate range (NOEs) consistent with a mixture of 3(10)-helix and alpha-helix. The relative intensities of the alpha N(i,i + 3) and alpha beta(i,i + 3) (nuclear Overhauser enhancements) NOEs suggest that 3(10)-helix is present throughout the peptide, but with the greatest contribution at the termini. A model was developed to determine the relative contributions of 3(10)-helix and alpha-helix. Lower bounds for the population of 3(10)-helix are approximately 50% at the termini and 25% in the middle of the peptide. The greatest alpha-helical content is between the middle of the peptide and the N terminus. (C) 1997 Academic Press Limited.
引用
收藏
页码:963 / 974
页数:12
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