Identification of the HIV-1 gp41 core-binding motif-HXXNPF

Identification of the HIV-1 gp41 core-binding motif-HXXNPF
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DOI:
10.1016/j.febslet.2006.07.067
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发表时间:
2006-09-04
期刊:
影响因子:
3.5
通讯作者:
Chen, Ying-Hua
Chen, Ying-Hua
中科院分区:
生物学3区
文献类型:
--
作者:
Huang, Jing-He;Liu, Zu-Qiang;Chen, Ying-Hua

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HIV-1 gp 41核心是在N-和C-末端七肽重复序列之间形成的六螺旋束,在病毒和靶细胞膜之间的融合中起关键作用。利用N36(L 8)C34作为gp 41核心的模型筛选噬菌体展示肽库,我们鉴定了一个共同的基序HXXNPF(X是20个天然氨基酸残基中的任一个)。筛选出的阳性噬菌体克隆L7.8与N36(L 8)C34特异性结合,这种结合可被gp 41核心特异性单克隆抗体(NC-1)阻断。含HXXNPF基序的多肽JCH-4能有效抑制HIV-1包膜糖蛋白介导的合胞体形成。JCH-4的抗原表位是线性的,可能位于gp 41核心的NHR区域。这些数据表明HXXNPF基序可能是一个gp 41核心结合序列,含HXXNPF基序的分子可作为研究HIV-1 gp 41核心在膜融合过程中作用的探针。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版,保留所有权利。
The HIV-1 gp41 core, a six-helix bundle formed between the N- and C-terminal heptad repeats, plays a critical role in fusion between the viral and target cell membranes. Using N36(L8)C34 as a model of the gp41 core to screen phage display peptide libraries, we identified a common motif, HXXNPF (X is any of the 20 natural amino acid residues). A selected positive phage clone L7.8 specifically bound to N36(L8)C34 and this binding could be blocked by a gp41 core-specific monoclonal antibody (NC-1). JCH-4, a peptide containing HXXNPF motif, effectively inhibited HIV-1 envelope glycoprotein-mediated syncytium-formation. The epitope of JCH-4 was proven to be linear and might locate in the NHR regions of the gp41 core. These data suggest that HXXNPF motif may be a gp41 core-binding sequence and HXXNPF motif-containing molecules can be used as probes for studying the role of the HIV-1 gp41 core in membrane-fusion process. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.