End Effects Influence Short Model Peptide Conformation

Abstract

Previously, we derived a P(II) propensity scale using N- and C-terminally blocked host-guest peptide model AcGGXGGNH(2) (X ≠ Gly) and concluded that P(II) represents a dominant conformation in the majority of this series of 19 peptides (Shi et al. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 17964-17968). Recently, Schweitzer-Stenner and co-workers examined a series of eight short host-guest tripeptides with the sequence GXG (X = A, V, F, S, E, L, M, and K) in which both N- and C-ends were unblocked and reported major differences in P(II) content for F, V, and S compared to our scale (Hagarman et al. J. Am. Chem. Soc. 2010, 132, 540-551). We have investigated four representative amino acids (X = A, V, F, and S) in three series of peptides (GXG, AcGXGNH(2), and AcGGXGGNH(2)) as a function of pH in this study. Our data show that P(II) content in the GXG series (X = A, V, F, and S) is pH-dependent and that the conformations of each amino acid differ markedly between the GXG and AcGXGNH(2)/AcGGXGGNH(2) series. Our results indicate that P(II) scales are sequence and context dependent and the presence of proximal charged end groups exerts a strong effect on P(II) population in short model peptides.

Conformational flexibility of PPII-helix: A density functional theory study

“…As terminal groups may have significant effects to structures of peptides [4,27,41], we replaced the N-terminal group to acetyl and formyl to estimate this effect. Compared to p-Br-benzoyl group, (Table S3).…”

Effects of phosphorylation on the intrinsic propensity of backbone conformations of serine/threonine

“…To study the intrinsic propensity toward a given local backbone conformation for a certain amino acid, people often used a simple dipeptide (ACE-X-NME, with X denoting a certain amino acid) or a host-guest peptide (GXG) to parameterize/characterize the interactions both experimentally and computationally [31][32][33]. In addition, the host-guest peptide AcGGXGGNH 2 was also frequently used [29,30,[34][35][36][37][38]. In the host-guest peptide AcGGXGGNH 2 , the glycines flanking residue X act as a spacer, which alleviates the influence of the end groups.…”

Solvation driven conformational transitions in the second transmembrane domain of mycobacteriophage holin

“…[23][24][25][26] They highlighted the ability of Ala-and Gly-containing short peptides to form PPII-like structures. [24][25][26][27][28][29] Such Pro -PPII structures play important roles in proteins. For example, they form the interdomain linker in calcium binding domains, 2,30 structure present in antigen epitope which binds to MHC class II, 31 and are seen in protein-nucleic acid interactions.…”