Conformation of a T cell stimulating peptide in aqueous solution

Abstract

Using two-dimensional NMR spectroscopy and circular dichroism spectroscopy it is demonstrated that a T cell stimulating peptide corresponding to residues 132-153 of sperm whale myoglobin populates helical conformations in aqueous solution. This finding is in accordance with proposals that immunodominant sites in T cell stimulating peptides have a high conformational propensity. The observation of secondary structure in aqueous solutions of this and other immunogenic peptides has important implications for initiation of protein folding.

Minute Time Scale Prolyl Isomerization Governs Antibody Recognition of an Intrinsically Disordered Immunodominant Epitope

“…9). It has been proposed that structural transitions within disordered regions could increase immunogenicity (58). Our data show that trans to cis isomerization of Pro-41 is a requirement for E7Ep⅐M1Fab complex formation (Scheme 1).…”

Molecular dynamics analysis of a ribonuclease C‐peptide analogue

“…The first considers systematic variation of synthetic, generally repetitive sequences in which relative helical stabilities can be measured, 5-10 or estimated from dynamics simulations.11~'4 A second strategy studies peptides having sequences of regions of secondary structure in particular proteins, in an attempt to understand features that lead to preferences for secondary structure in very nonrepetitive sequences. This approach is illustrated by recent nmr studies on peptides derived from myoglobin, ribonuclease, plastocyanin, and myohemerythrin, [15][16][17][18][19] as well as by extensive theoretical simulations on the ribonuclease and myoglobin peptides?0,21 Here we follow the latter path, reporting details of a nanosecond molecular dynamics simulation of a variant ("RNM") of the ribonuclease C-peptide. The results may be compared to our earlier simulations on the myoglobin H helix, 21 to earlier theoretical studies on similar sequences," and to nmr studies.…”

Structural Characterization of a Partly Folded Apomyoglobin Intermediate

“…Peptides with sequences corresponding to the H helix are substantially helical in aqueous solution (19,20), demonstrating that important determinants of native structure reside at the local secondary structure level and act independently of higher order Fig. 4 interactions.…”