Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1IIIb and an O‐glycosylated analogue

FEBS Letters

Berzofsky, Jay A.²  Charles Smith, M.²  Barchi, Joseph J.¹  Huang, Xiaolin¹ 

[1]Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

[2]Molecular Immunogenetics and Vaccine Research Section, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

关键词: NMR;    V3 loop;    Glycopeptide;    CTL;   

DOI  :  10.1016/0014-5793(96)00912-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

As part of a program to study the effect of glycosylation on the three-dimensional structures of HIV-1 _IIIB V3 peptide constructs, we have examined the solution structures of a 15 residue peptide (RIQRGPGRAFVTIGK, P18 _IIIB ), originally mapped as an epitope recognized by CD8⁺ D ^d class I MHC-restricted murine cytotoxic T-lymphocytes (CTL), and an analogue (P18 _IIIB -g), O-glycosylated with an α-galactosamine on Thr-12, using NMR, circular dichroism and molecular modeling methods. Our studies show that the peptides sample mainly random conformations in aqueous solution near 25°C and become more ordered by the addition of trifluoroethanol. Upon decreasing the temperature to 5°C, a reverse turn is formed around the immunodominant tip (G⁵−R⁸). Glycosylation on T¹² ‘tightens’ the turn slightly as suggested by NOE and CD analysis. In addition, the sugar has a defined conformation with respect to the peptide backbone and influences the local peptide conformation. These data suggest that simple glycosylation may influence the conformational equilibrium of a V3 peptide which contains a domain critical for antibody recognition and virus neutralization. We also show that the ability of cytotoxic T-lymphocytes (CTL) to lyse tumor cells presenting P18 _IIIB was completely abrogated by threonine glycosylation.

【 授权许可】

Unknown