A noncanonical mu-1A-binding motif in the N terminus of HIV-1 Nef determines its ability to downregulate major histocompatibility complex class I in T lymphocytes.
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.
Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Hachimandai, Tsukuba-shi, Ibaraki, Japan.
Sayuki
S
Iijima
Young-Jung
YJ
Lee
Hirotaka
H
Ode
Stefan T
ST
Arold
Nobuyuki
N
Kimura
Masaru
M
Yokoyama
Hironori
H
Sato
Yasuhito
Y
Tanaka
Klaus
K
Strebel
Hirofumi
H
Akari
D033961:Adaptor Protein Complex 1 / Q000235:genetics / Q000378:metabolism*; D033983:Adaptor Protein Complex mu Subunits / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C438883:AP1M1 protein, human; D033961:Adaptor Protein Complex 1; D033983:Adaptor Protein Complex mu Subunits; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1