The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes

Greenberg, M. E., Iafrate, A. J., Skowronski, J. (May 1998) The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes. Embo Journal, 17 (10). pp. 2777-89. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/9582271
DOI: 10.1093/emboj/17.10.2777

Abstract

Nef, a regulatory protein of human and simian immunodeficiency viruses, downregulates cell surface expression of both class I MHC and CD4 molecules in T cells by accelerating their endocytosis. Fibroblasts were used to study alterations in the traffic of class I MHC complexes induced by Nef. We found that Nef downregulates class I MHC complexes by a novel mechanism involving the accumulation of endocytosed class I MHC in the trans-Golgi, where it colocalizes with the adaptor protein-1 complex (AP-1). This effect of Nef on class I MHC traffic requires the SH3 domain-binding surface and a cluster of acidic amino acid residues in Nef, both of which are also required for Nef to downregulate class I MHC surface expression and to alter signal transduction in T cells. Downregulation of class I MHC complexes from the surface of T cells also requires a tyrosine residue in the cytoplasmic domain of the class I MHC heavy chain molecule. The requirement of the same surfaces of the Nef molecule for downregulation of surface class I MHC complexes in T cells and for their accumulation in the trans-Golgi of fibroblasts indicates that the two effects of Nef involve similar interactions with the host cell machinery and involve a molecular mechanism regulating class I MHC traffic that is common for both of these cell types. Interestingly, the downregulation of class I MHC does not require the ability of Nef to colocalize with the adaptor protein-2 complex (AP-2). We showed previously that the ability of Nef to colocalize with AP-2 correlates with the ability of Nef to downregulate CD4 expression. Our observations indicate that Nef downregulates class I MHC and CD4 surface expression via different interactions with the protein sorting machinery, and link the sorting and signal transduction machineries in the regulation of class I MHC surface expression by Nef.

Item Type: Paper
Uncontrolled Keywords: Adaptor Protein Complex alpha Subunits Adaptor Proteins, Vesicular Transport Antigens, CD4/metabolism Binding Sites Cell Membrane/metabolism Cells, Cultured Down-Regulation Gene Expression Gene Products, nef/genetics/ metabolism Golgi Apparatus/metabolism HIV-1/ metabolism HLA-B7 Antigen/metabolism Histocompatibility Antigens Class I/ metabolism Humans Jurkat Cells Membrane Proteins/metabolism Recombinant Fusion Proteins/genetics/metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Tyrosine/metabolism src Homology Domains
Subjects: diseases & disorders > viral diseases > HIV
Investigative techniques and equipment > cell culture
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > SH3 domain
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Skowronski lab
Depositing User: Kathleen Darby
Date: 15 May 1998
Date Deposited: 01 May 2014 19:57
Last Modified: 01 May 2014 19:57
PMCID: PMC1170618
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29886

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