Virus-cell and cell-cell fusion mediated by the HIV-1 envelope glycoprotein is inhibited by short gp41 N-terminal membrane-anchored peptides lacking the critical pocket domain

Article

关键词: TRIMERIC COILED-COIL;    IMMUNODEFICIENCY-VIRUS;    POTENT INHIBITORS;    CORE STRUCTURE;    ENTRY;    TYPE-1;    SURFACE;    DESIGN;    REGION;    STABILIZATION;   

DOI  :  10.1096/fj.09-151704

来源: SCIE

【 摘 要 】

The interactions between the N- and C-terminal heptad repeat (NHR and CHR) regions of the human immunodeficiency virus (HIV-1) glycoprotein gp41 create a structure comprising a 6-helix bundle (SHB). A sequence in the SHB named the pocket is crucial for the SHB's stability and for the fusion inhibitory activity of 36-residue NHR peptide N36. We report that a short 27-residue peptide, N27, which lacks the pocket sequence, exhibits potent inhibitory activity in both cell-cell and virus-cell fusion assays when fatty acids were conjugated to its N but not C terminus. Furthermore, mutations in the positions that prevent interaction with the CHR but not with the NHR resulted in a dramatic reduction in N27 activity. These data support a mechanism in which N27 mainly targets the CHR rather than the internal NHR coiled-coil, reveal the N-terminal edge of the endogenous core structure in situ and hence complement our recent findings of the C-terminal edge of the core, and provide a new approach for designing short inhibitors from the NHR region of other lentiviruses due to similarities in their envelope proteins.-Wexler-Cohen, Y., Ashkenazi, A., Viard, M., Blumenthal, R., Shai, Y. Virus-cell and cell-cell fusion mediated by the HIV-1 envelope glycoprotein is inhibited by short gp41 N-terminal membrane-anchored peptides lacking the critical pocket domain. FASEB J. 24, 4196-4202 (2010). www.fasebj.org

【 授权许可】

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