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)
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: | https://repository.cshl.edu/id/eprint/29817 |
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