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J. Biol. Chem., Vol. 283, Issue 22, 14994-15002, May 30, 2008
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2
From the
Laboratory of Immunology, Department of Biology, Tsinghua University, Protein Science Laboratory of the Ministry of Education, Beijing 100084, China, ¶Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, and
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129
The human immunodeficiency virus, type 1 (HIV-1), gp41 core plays an important role in fusion between viral and target cell membranes. We previously identified an HIV-1 gp41 core-binding motif HXXNPF (where X is any amino acid residue). In this study, we found that Asn, Pro, and Phe were the key residues for gp41 core binding. There are two NPF motifs in Epsin-1-(470–499), a fragment of Epsin, which is an essential accessory factor of endocytosis that can dock to the plasma membrane by interacting with the lipid. Epsin-1-(470–499) bound significantly to the gp41 core formed by the polypeptide N36(L8)C34 and interacted with the recombinant soluble gp41 containing the core structure. A synthetic peptide containing the Epsin-1-(470–499) sequence could effectively block entry of HIV-1 virions into SupT1 T cells via the endocytosis pathway. These results suggest that interaction between Epsin and the gp41 core, which may be present in the target cell membrane, is probably essential for endocytosis of HIV-1, an alternative pathway of HIV-1 entry into the target cell.
Received for publication, January 22, 2008 , and in revised form, March 26, 2008.
* This work was supported, in whole or in part, by National Institutes of Health Grant AI46221 (to S. J.). This work was also supported by the Emphases Project of the Natural Science Foundation of China NSFC-30530680 and 2007CB914402 (to Y. H. C.). 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. 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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