Abstract
Downregulation of major histocompatibility complex class I (MHC-I) by HIV-1 Nef protein is indispensable for evasion of protective immunity by HIV-1. Though it has been suggested that the N-terminal region of Nef contributes to the function by associating with a mu-1A subunit of adaptor protein 1, the structural basis of the interaction between Nef and mu-1A remains elusive. We found that a tripartite hydrophobic motif (Trp13/Val16/Met20) in the N terminus of Nef was required for the MHC-I downregulation. Importantly, the motif functioned as a noncanonical mu-1A-binding motif for the interaction with the tyrosine motif-binding site of the mu-1A subunit. Our findings will help understanding of how HIV-1 evades the antiviral immune response by selectively redirecting the cellular protein trafficking system.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Protein Complex 1 / genetics
-
Adaptor Protein Complex 1 / metabolism*
-
Adaptor Protein Complex mu Subunits / genetics
-
Adaptor Protein Complex mu Subunits / metabolism*
-
Amino Acid Motifs
-
Amino Acid Sequence
-
Binding Sites
-
Down-Regulation*
-
HIV Infections / genetics
-
HIV Infections / metabolism*
-
HIV Infections / virology
-
HIV-1 / chemistry
-
HIV-1 / genetics
-
HIV-1 / metabolism*
-
Histocompatibility Antigens Class I / genetics*
-
Histocompatibility Antigens Class I / metabolism
-
Humans
-
Molecular Sequence Data
-
Protein Binding
-
T-Lymphocytes / metabolism*
-
T-Lymphocytes / virology
-
nef Gene Products, Human Immunodeficiency Virus / chemistry*
-
nef Gene Products, Human Immunodeficiency Virus / genetics
-
nef Gene Products, Human Immunodeficiency Virus / metabolism*
Substances
-
AP1M1 protein, human
-
Adaptor Protein Complex 1
-
Adaptor Protein Complex mu Subunits
-
Histocompatibility Antigens Class I
-
nef Gene Products, Human Immunodeficiency Virus
-
nef protein, Human immunodeficiency virus 1