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Originally published In Press as doi:10.1074/jbc.M607701200 on December 31, 2006

J. Biol. Chem., Vol. 282, Issue 9, 6143-6152, March 2, 2007
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Identification of the HIV-1 gp41 Core-binding Motif in the Scaffolding Domain of Caveolin-1*

Jing-He Huang{ddagger}, Lu Lu{ddagger}, Hong Lu§, Xi Chen{ddagger}, Shibo Jiang§1, and Ying-Hua Chen{ddagger}2

From the {ddagger}Laboratory of Immunology, Department of Biology, Tsinghua University, Protein Science Laboratory of the Ministry of Education, Beijing 100084, P.R. China and the §Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021

The human immunodeficiency virus, type 1 (HIV-1) gp41 core plays an important role in fusion between viral and target cell membranes. A single chain polypeptide, N36(L8)C34, which forms a six-helix bundle in physiological solution, can be used as a model of gp41 core. Here we identified from a 12-mer phage peptide library a positive phage clone displaying a peptide sequence with high binding activity to the HIV-1 gp41 core. The peptide sequence contains a putative gp41-binding motif, {Phi}XXXX{Phi}X{Phi} (X is any amino acid residue, and {Phi} is any one of the aromatic amino acid residues Trp, Phe, or Tyr). This motif also exists in the scaffolding domain of caveolin-1 (Cav-1), a known gp41-binding protein. Cav-1-(61–101) and Cav-1-(82–101), two recombinant fusion proteins containing the Cav-1 scaffolding domain, bound significantly to the gp41 expressed in mammalian cells and interacted with the polypeptide N36(L8)C34. These results suggest that the scaffolding domain of Cav-1 may bind to the gp41 core via the motif. This interaction may be essential for formation of fusion pore or endocytosis of HIV-1 and affect the pathogenesis of HIV-1 infection. Further characterization of the gp41 core-binding motifs may shed light on the alternative mechanism by which HIV-1 enters into the target cell.


Received for publication, August 11, 2006 , and in revised form, December 28, 2006.

* This work was supported by the Emphases Project (Grants NSFC-30530680 and NSFC-30221003 to Y. H. C.) and by National Institutes of Health (NIH) Grant AI46221 (to S. J.). The cell lines 3T3.T4.CXCR4, CHO-WT, and CHO-EE were obtained from the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH and contributed by Drs. Dan R. Littman, Carol Weiss, and Judith White, respectively. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence may be addressed: Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021. Tel.: 212-570-3058; Fax: 212-570-3099; E-mail: sjiang{at}nybloodcenter.org. 2 To whom correspondence may be addressed: Tel.: 86-10-6277-2267; Fax: 86-10-6277-1613; E-mail: chenyh{at}mail.tsinghua.edu.cn.


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