Zinc binding site of HIV-2 Vpx prevents instability and dysfunction of the protein.
Zinc binding site of HIV-2 Vpx prevents instability and dysfunction of the protein.
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DOI：
10.1099/jgv.0.000701
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
Minami Yamamoto;Ryoko Koga;Haruna Fujino;Kazunori Shimagaki;Halil I. Ciftci;Masahiro Kamo;Hiroshi Tateishi;M. Otsuka;M. Fujita
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文献类型：
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作者：
Minami Yamamoto;Ryoko Koga;Haruna Fujino;Kazunori Shimagaki;Halil I. Ciftci;Masahiro Kamo;Hiroshi Tateishi;M. Otsuka;M. Fujita
HIV-2 Vpx通过残基H39、H82、C87和C89与锌配位。我们以前报道，H39，H82和C87突变体保持Vpx活性，以促进SAMHD 1的降解。在此，详细检查了Vpx突变体在细胞中的表达。我们证明，锌结合位点稳定蛋白质，以保持其功能，在病毒生长时，低水平的Vpx表达。在更高的表达水平下，Vpx聚集可以发生，并且锌结合将抑制这种聚集。在参与锌配位的氨基酸中，H39起着最关键的作用。总之，锌结合似乎减轻Vpx的三螺旋折叠的灵活性，从而防止功能障碍。
HIV-2 Vpx coordinates zinc through residues H39, H82, C87 and C89. We reported previously that H39, H82 and C87 mutants maintain Vpx activity to facilitate the degradation of SAMHD1. Herein, the expression of Vpx mutants in cells was examined in detail. We demonstrated that the zinc-binding site stabilizes the protein to keep its function in virus growth when low levels of Vpx are expressed. At higher levels of expression, Vpx aggregation can occur, and zinc binding would suppress such aggregation. Among the amino acids involved in zinc coordination, H39 plays the most critical role. In summary, zinc binding appears to mitigate flexibility of the three-helix fold of Vpx, thereby preventing dysfunction.