Induction of a nonproductive conformational change in gp120 by a small molecule HIV type 1 entry inhibitor

被引：13

作者：

Huang, Li ^{[1
]}

Lai, Weihong ^{[1
]}

Ho, Phong ^{[1
]}

Chen, Chin Ho ^{[1
]}

机构：

[1] Duke Univ, Ctr Med, Dept Surg, Durham, NC 27710 USA

来源：

AIDS RESEARCH AND HUMAN RETROVIRUSES | 2007年 / 23卷 / 01期

关键词：

D O I：

10.1089/aid.2006.0137

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Conformational changes in HIV-1 envelope glycoproteins, gp120 and gp41, is a dynamic process essential for HIV-1 entry. Here we show that a small molecule HIV-1 entry inhibitor, IC9564, induces a conformational change in gp120. The conformational change in gp120 is evidenced by a significant increase in the binding of a conformational monoclonal antibody 17b. As a result of the conformational effect, IC9564 significantly enhances the neutralizing activity of 17b. Unlike CD4, IC9564 does not trigger conformational changes in gp41. In fact, IC9564 inhibits CD4-induced conformational changes in gp41. Thus, IC9564 exploits the dynamic nature of gp120 by inducing a nonproductive gp120 conformation that is not able to trigger a conformational change in gp41 for membrane fusion.

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页码：28 / 32

页数：5

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