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The Human Thioesterase II Protein Binds to a Site on HIV-1 Nef Critical for CD4 Down-regulation

Cohen, George B. and Rangan, Vangipuram S. and Chen, Benjamin K. and Smith, Stuart and Baltimore, David (2000) The Human Thioesterase II Protein Binds to a Site on HIV-1 Nef Critical for CD4 Down-regulation. Journal of Biological Chemistry, 275 (30). pp. 23097-23105. ISSN 0021-9258. doi:10.1074/jbc.M000536200.

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A HIV-1 Nef affinity column was used to purify a 35-kDa Nef-interacting protein from T-cell lysates. The 35-kDa protein was identified by peptide microsequence analysis as the human thioesterase II (hTE) enzyme, an enzyme previously identified in a yeast two-hybrid screen as a potential Nef-interacting protein. Immunofluorescence studies showed that hTE localizes to peroxisomes and that coexpression of Nef and hTE leads to relocalization of Nef to peroxisomes. Interaction of Nef and hTE was abolished by point mutations in Nef at residues Asp108, Leu112, Phe121, Pro122, and Asp123. All of these mutations also abrogated the ability of Nef to down-regulate CD4 from the surface of HIV-infected cells. Based on the x-ray and NMR structures of Nef, these residues define a surface on Nef critical for CD4 down-regulation. A subset of these mutations also affected the ability of Nef to down-regulate major histocompatibility complex class I. These results, taken together with previous studies, identify a region on Nef critical for most of its known functions. However, not all Nef alleles bind to hTE with high affinity, so the role of hTE during HIV infection remains uncertain.

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Baltimore, David0000-0001-8723-8190
Additional Information:Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, January 21, 2000, and in revised form, May 2, 2000. Originally published In Press as doi:10.1074/jbc.M000536200 on May 11, 2000. We thank members of the Baltimore lab for helpful discussions and Bruce Walker, Richard Benarous, Joseph Budman, Sandra L. Hofmann, Merilyn D. Resh, Chi-Hon Lee, and Richard Cook for reagents and help on aspects of this project. This work was supported by a Merck/MIT and Helen-Hay Whitney Fellowships (to G.B.C.) and a grant from the Children's Hospital Oakland Research Institute Endowment (to V.S.R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. [D.B. was an] American Cancer Society Research Professor. Supported by grants from the National Institutes of Health.
Issue or Number:30
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ID Code:10716
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Deposited On:04 Jun 2008
Last Modified:08 Nov 2021 21:10

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