鸟嘌呤核苷酸交换因子 RCC1 促进脑心肌炎病毒的先导与细胞内 Ran GTP 酶的紧密结合。
Guanine-nucleotide exchange factor RCC1 facilitates a tight binding between the encephalomyocarditis virus leader and cellular Ran GTPase.
机构信息
Department of Biochemistry, Institute for Molecular Virology, University of Wisconsin, Madison, Wisconsin, USA.
出版信息
J Virol. 2013 Jun;87(11):6517-20. doi: 10.1128/JVI.02493-12. Epub 2013 Mar 27.
Abstract
The leader (L) protein of encephalomyocarditis virus (EMCV) shuts off host cell nucleocytoplasmic trafficking (NCT) by inducing hyperphosphorylation of nuclear pore proteins. This dramatic effect by a nonenzymatic protein of 6 kDa is not well understood but clearly involves L binding to cellular Ran GTPase, a critical factor of active NCT. Exogenous GDP and GTP are inhibitory to L-Ran binding, but the guanine-nucleotide exchange factor RCC1 can relieve this inhibition. In the presence of RCC1, L binds Ran with a KD (equilibrium dissociation constant) of ≈ 3 nM and reaches saturation within 20 min. The results of fluorescently tagged nucleotide experiments suggest that L-Ran interactions affect the nucleotide-binding pocket of Ran.
摘要
脑心肌炎病毒（EMCV）的 L 蛋白通过诱导核孔蛋白的过度磷酸化来阻断宿主细胞的核质转运（NCT）。这种由 6 kDa 的非酶蛋白引起的显著效应尚不清楚，但显然涉及 L 与细胞 Ran GTPase 的结合，Ran GTPase 是活跃的 NCT 的关键因素。外源 GDP 和 GTP 对 L-Ran 结合有抑制作用，但 G 核苷酸交换因子 RCC1 可以解除这种抑制。在 RCC1 存在的情况下，L 与 Ran 的结合 KD（平衡解离常数）约为 3 nM，并且在 20 分钟内达到饱和。荧光标记核苷酸实验的结果表明，L-Ran 相互作用影响 Ran 的核苷酸结合口袋。
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