Two elements target SIV Nef to the AP-2 clathrin adaptor complex, but only one is required for the induction of CD4 endocytosis

Lock, M., Greenberg, M. E., Iafrate, A. J., Swigut, T., Muench, J., Kirchhoff, F., Shohdy, N., Skowronski, J. (May 1999) Two elements target SIV Nef to the AP-2 clathrin adaptor complex, but only one is required for the induction of CD4 endocytosis. Embo Journal, 18 (10). pp. 2722-33. ISSN 0261-4189 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/10329619
DOI: 10.1093/emboj/18.10.2722

Abstract

The simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) Nef proteins induce the endocytosis of CD4 and class I MHC molecules. Here we show that SIV Nef interacts with the AP-2 adaptor complex via two elements located in the N-terminal region of the Nef molecule, but only the N-distal element is required to induce CD4 endocytosis. This N-distal AP-2 targeting element contains no canonical endocytic signals and probably contacts the AP-2 complex via a novel interaction surface. The data support a model where SIV Nef induces CD4 endocytosis by promoting the normal interactions between the di-leucine sorting signal in the CD4 cytoplasmic domain and AP-2, but does not substitute for the CD4-AP-2 adaptor interaction. Neither element is important for the induction of class I MHC endocytosis, thus indicating that different mechanisms underlie the induction of class I MHC and CD4 endocytosis by Nef. In contrast to SIV Nef, HIV-1 Nef interacts with AP-2 via a surface containing a di-leucine endocytosis signal in the C-terminal disordered loop of Nef. The fact that genetic selection maintains similar molecular interactions via different surfaces in SIV and HIV-1 Nef proteins indicates that these interactions have critical roles for the viral life cycle in vivo.

Item Type: Paper
Uncontrolled Keywords: Adaptor Proteins, Vesicular Transport Amino Acid Sequence Antigens, CD4/metabolism Base Sequence Clathrin/metabolism Down-Regulation Endocytosis Fibroblasts Gene Products, nef/chemistry/genetics/ metabolism Green Fluorescent Proteins HIV-1/metabolism Histocompatibility Antigens Class I/immunology/metabolism Humans Jurkat Cells Luminescent Proteins Molecular Sequence Data Mutation Nerve Tissue Proteins/ metabolism Phosphoproteins/ metabolism Protein Binding Recombinant Fusion Proteins/genetics Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Simian immunodeficiency virus/ metabolism Tyrosine/genetics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
diseases & disorders > viral diseases > SIV
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > green fluorescent protein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Skowronski lab
Depositing User: Kathleen Darby
Date: 17 May 1999
Date Deposited: 28 Apr 2014 16:38
Last Modified: 30 Apr 2014 17:52
PMCID: PMC1171354
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29817

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