Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression.

Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression.
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DOI:
10.1016/j.virol.2009.10.048
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发表时间:
2010-02-05
期刊:
影响因子:
3.7
通讯作者:
Stephens, Edward B.
Stephens, Edward B.
中科院分区:
医学3区
文献类型:
--
作者:
Hill, M. Sarah;Ruiz, Autumn;Schmitt, Kimberly;Stephens, Edward B.

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Human immunodeficiency virus type 1 (HIV-1) encodes for a Vpu protein, which interacts with CD4 resulting in its degradation. In this study, we examined the role of the ten amino acids within the predicted second α-helical domain of the subtype B Vpu cytoplasmic tail in CD4 down-modulation using a VpuEGFP reporter system. Our findings indicate that the invariant leucine at position 63 and, to a lesser extent, the valine at position 68 were required for CD4 down-modulation. Mutation of analogous L63 in Vpu proteins subtypes A2, B, C, D, and H also abolished CD4 down-modulation from the cell surface. Co-immunoprecipitation analysis revealed that L63A and V68A mutants were capable of binding CD4 and still retained the ability to interact with h-β-TrCP1. Taken together, these results indicate that amino acid substitutions in the second α-helical domain that retain the predicted structure and binding to h-β-TrCP1 can influence Vpu-mediated CD4 degradation.
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