title: Induction of a nonproductive conformational change in gp120 by a small molecule HIV type 1 entry inhibitor.
abstract: 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.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Weihong
authors.initials: W
authors.lastname: Lai
authors.forename: Phong
authors.initials: P
authors.lastname: Ho
authors.forename: Chin Ho
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000187:drug effects*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry; D023581:HIV Fusion Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009500:Neutralization Tests; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects*; D014162:Transfection; D014315:Triterpenes / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; C419364:IC9564; D014315:Triterpenes