Endocytic activity of HIV-1 Vpu: Phosphoserine-dependent interactions with clathrin adaptors.
Endocytic activity of HIV-1 Vpu: Phosphoserine-dependent interactions with clathrin adaptors.
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DOI：
10.1111/tra.12495
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Guatelli J
中科院分区：
文献类型：
--
作者：
Stoneham CA;Singh R;Jia X;Xiong Y;Guatelli J
HIV-1 Vpu调节细胞跨膜蛋白以优化病毒复制并提供免疫逃避，触发某些靶标的泛素介导的降解，但也调节内体运输以将其从质膜上耗尽。已经描述了Vpu和异四聚体网格蛋白衔接子AP-1和AP-2之间的相互作用，但这种相互作用的分子基础和功能作用尚未完全确定。为了研究Vpu编码的运输信号，我们将Vpu的胞质结构域（CD）融合到CD 8 α链的胞外和跨膜结构域。CD 8-VpuCD以网格蛋白和AP-2依赖性方式被快速内吞。Vpu CD内的多个决定簇有助于内吞活性，包括β-TrCP结合位点的磷酸丝氨酸和基于亮氨酸的ExxxLV基序。使用重组蛋白，我们证实了Vpu CD与AP-2的α/σ2亚基半复合物的ExxxLV依赖性结合，并表明丝氨酸磷酸化增强了这种结合。值得注意的是，Vpu CD还直接结合AP-2和AP-1的中（μ）亚基;这种相互作用依赖于Vpu的丝氨酸磷酸化和μ亚基中的碱性残基。我们认为，Vpu与AP复合物结合的灵活性扩大了细胞靶点的范围，从而使其误导病毒的优势。
HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune-evasion, triggering ubiquitin-mediated degradation of some targets but also modulating endosomal trafficking to deplete them from the plasma membrane. Interactions between Vpu and the heterotetrameric clathrin adaptors AP-1 and AP-2 have been described, yet the molecular basis and functional roles of such interactions are incompletely defined. To investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8 α-chain. CD8-VpuCD was rapidly endocytosed in a clathrin- and AP-2-dependent manner. Multiple determinants within the Vpu CD contributed to endocytic activity, including phosphoserines of the β-TrCP binding site and a leucine-based ExxxLV motif. Using recombinant proteins, we confirmed ExxxLV-dependent binding of the Vpu CD to the α/σ2 subunit hemicomplex of AP-2 and showed that this is enhanced by serine-phosphorylation. Remarkably, the Vpu CD also bound directly to the medium (μ) subunits of AP-2 and AP-1; this interaction was dependent on serine-phosphorylation of Vpu and on basic residues in the μ subunits. We propose that the flexibility with which Vpu binds AP complexes broadens the range of cellular targets that it can misdirect to the virus’s advantage.
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影响因子：
32.4
作者：
BAUR, AS;SAWAI, ET;PETERLIN, BM
通讯作者：
PETERLIN, BM
影响因子：
6.7
作者：
Janvier K;Pelchen-Matthews A;Renaud JB;Caillet M;Marsh M;Berlioz-Torrent C
通讯作者：
Berlioz-Torrent C
影响因子：
7.8
作者：
Hirst, J;Lui, W W;Bright, N A;Totty, N;Seaman, M N;Robinson, M S
通讯作者：
Robinson, M S
DOI：
10.1083/jcb.135.2.341
发表时间：
1996-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Marks MS;Woodruff L;Ohno H;Bonifacino JS
通讯作者：
Bonifacino JS
影响因子：
16.8
作者：
Jia, Xiaofei;Singh, Rajendra;Homann, Stefanie;Yang, Haitao;Guatelli, John;Xiong, Yong
通讯作者：
Xiong, Yong