Direct Binding of Human Immunodeficiency Virus Type 1 Nef to the Major Histocompatibility Complex Class I (MHC-I) Cytoplasmic Tail Disrupts MHC-I Trafficking
| Autor: | Jeremiah F. Roeth, Matthew R. Kasper, Kathleen L. Collins, Chris G. Przybycin, Rebekah I. Fleis, Maya Williams |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Recombinant Fusion Proteins
viruses Molecular Sequence Data Immunology DNA Recombinant chemical and pharmacologic phenomena Plasma protein binding Human leukocyte antigen Major histocompatibility complex Models Biological Microbiology Gene Products nef Cell Line Mice HLA Antigens Virology HLA-A2 Antigen MHC class I Animals Humans Cytotoxic T cell Amino Acid Sequence nef Gene Products Human Immunodeficiency Virus Peptide sequence Cell Nucleus Binding Sites Base Sequence biology Histocompatibility Antigens Class I H-2 Antigens CD28 In vitro Protein Structure Tertiary Virus-Cell Interactions Cell biology Insect Science DNA Viral HIV-1 Mutagenesis Site-Directed biology.protein HeLa Cells Protein Binding |
| Zdroj: | Journal of Virology. 76:12173-12184 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.76.23.12173-12184.2002 |
| Popis: | Nef, an essential pathogenic determinant for human immunodeficiency virus type 1, has multiple functions that include disruption of major histocompatibility complex class I molecules (MHC-I) and CD4 and CD28 cell surface expression. The effects of Nef on MHC-I have been shown to protect infected cells from cytotoxic T-lymphocyte recognition by downmodulation of a subset of MHC-I (HLA-A and -B). The remaining HLA-C and -E molecules prevent recognition by natural killer (NK) cells, which would otherwise lyse cells expressing small amounts of MHC-I. Specific amino acid residues in the MHC-I cytoplasmic tail confer sensitivity to Nef, but their function is unknown. Here we show that purified Nef binds directly to the HLA-A2 cytoplasmic tail in vitro and that Nef forms complexes with MHC-I that can be isolated from human cells. The interaction between Nef and MHC-I appears to be weak, indicating that it may be transient or stabilized by other factors. Supporting the fact that these molecules interact in vivo, we found that Nef colocalizes with HLA-A2 molecules in a perinuclear distribution inside cells. In addition, we demonstrated that Nef fails to bind the HLA-E tail and also fails to bind HLA-A2 tails with deletions of amino acids necessary for MHC-I downmodulation. These data provide an explanation for differential downmodulation of MHC-I allotypes by Nef. In addition, they provide the first direct evidence indicating that Nef functions as an adaptor molecule able to link MHC-I to cellular trafficking proteins. |
| Databáze: | OpenAIRE |
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