丝氨酸-苏氨酸泛素化介导 BST-2/ tetherin 的下调和 HIV-1 Vpu 缓解病毒粒子释放的限制。
Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu.
机构信息
Department of Medicine University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0679, USA.
出版信息
J Virol. 2011 Jan;85(1):51-63. doi: 10.1128/JVI.01795-10. Epub 2010 Oct 27.
Abstract
The HIV-1 protein Vpu counteracts the antiviral activity of the innate restriction factor BST-2/tetherin by a mechanism that partly depends on its interaction with β-TrCP, a substrate adaptor for an SCF (Skp-Cullin 1-F box) E3 ubiquitin ligase complex. This suggests that Vpu stimulates the ubiquitination of BST-2 and that this underlies the relief of restriction. Here, we show that Vpu stimulates ubiquitination of BST-2. Mutation of all potential ubiquitination sites in the cytoplasmic domain of BST-2, including lysines, cysteines, serines, and threonines, abrogates Vpu-mediated ubiquitination. However, a serine-threonine-serine sequence specifically mediates the downregulation of BST-2 from the cell surface and the optimal relief of restricted virion release. Serine-threonine ubiquitination of BST-2 is likely part of the mechanism by which Vpu counteracts innate defenses.
摘要
HIV-1 蛋白 Vpu 通过一种部分依赖于其与 β-TrCP 相互作用的机制来拮抗先天限制因子 BST-2/ tetherin 的抗病毒活性，β-TrCP 是一种 SCF（Skp-Cullin 1-F box）E3 泛素连接酶复合物的底物衔接子。这表明 Vpu 刺激 BST-2 的泛素化，而这是限制缓解的基础。在这里，我们表明 Vpu 刺激 BST-2 的泛素化。BST-2 细胞质结构域中所有潜在泛素化位点（包括赖氨酸、半胱氨酸、丝氨酸和苏氨酸）的突变都消除了 Vpu 介导的泛素化。然而，丝氨酸-苏氨酸-丝氨酸序列特异性介导 BST-2 从细胞表面下调和限制的病毒粒子释放的最佳缓解。BST-2 的丝氨酸-苏氨酸泛素化可能是 Vpu 拮抗先天防御的机制的一部分。
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