Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Hachimandai, Tsukuba-shi, Ibaraki, Japan.
J Virol. 2012 Apr;86(7):3944-51. doi: 10.1128/JVI.06257-11. Epub 2012 Feb 1.
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.
HIV-1 Nef 蛋白下调主要组织相容性复合体 I（MHC-I）对于 HIV-1 逃避保护性免疫是必不可少的。尽管有人提出 Nef 的 N 端区域通过与衔接蛋白 1 的 mu-1A 亚基结合来发挥作用，但 Nef 和 mu-1A 之间相互作用的结构基础仍不清楚。我们发现 Nef N 端的三部分疏水性基序（Trp13/Val16/Met20）对于 MHC-I 的下调是必需的。重要的是，该基序作为非典型的 mu-1A 结合基序，与 mu-1A 亚基的酪氨酸基序结合位点相互作用。我们的发现将有助于理解 HIV-1 如何通过选择性地重新定向细胞蛋白运输系统来逃避抗病毒免疫反应。
