A Short Lipopeptide Derived from the N-Heptad Repeat Region Inhibits HIV-1 Gp41 Mediated Fusion Via an Altered Mode of Action
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چکیده
منابع مشابه
Membrane-Anchored HIV-1 N-Heptad Repeat Peptides Are Highly Potent Cell Fusion Inhibitors via an Altered Mode of Action
Peptide inhibitors derived from HIV-gp41 envelope protein play a pivotal role in deciphering the molecular mechanism of HIV-cell fusion. According to accepted models, N-heptad repeat (NHR) peptides can bind two targets in an intermediate fusion conformation, thereby inhibiting progression of the fusion process. In both cases the orientation towards the endogenous intermediate conformation shoul...
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During HIV-1 fusion to the host cell membrane, the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR) of the envelope subunit gp41 become transiently exposed and accessible to fusion inhibitors or Abs. In this process, the NHR region adopts a trimeric coiled-coil conformation that can be a target for therapeutic intervention. Here, we present an approach to rationally design ...
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To prove that the peptidic HIV-1 fusion inhibitors containing the pocket-binding domain (PBD) mainly target the hydrophobic pocket in the gp41 N-terminal heptad repeat (NHR), we constructed pseudoviruses by replacement of Q64 in the gp41 pocket region with Ala (Q64A) or Leu (Q64L). These viruses were highly resistant to C34 and CP32M containing the PBD, while they were susceptible to T20 (enfuv...
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The spectrum of inhibition of human (HIV) and simian (SIV) immunodeficiency virus envelope (Env)-mediated cell fusion by C34, a 34 residue peptide corresponding to the C-heptad repeat of gp41 (residues 628-661 of HIV-1 Env), has been examined using a panel of five envelope glycoproteins, three from HIV-1 (LAV, SF162 and 89.6) and two from SIV (mac239 and mac316), and six C34 peptides derived fr...
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During human immunodeficiency virus entry, gp41 undergoes a series of conformational changes that induce membrane fusion. Immediately prior to fusion, gp41 exists in a prehairpin intermediate in which the N- and C-peptide regions of gp41 are exposed. Rearrangement of this intermediate into a six-helix bundle composed of a trimeric coiled coil from the N-peptide region (N-trimer) surrounded by t...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2010
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2009.12.3682