Zhang Xinsheng, Bourhis Jean-Marie, Longhi Sonia, Carsillo Thomas, Buccellato Matthew, Morin Benjamin, Canard Bruno, Oglesbee Michael
Department of Veterinary Biosciences, The Ohio State University, Columbus, 43210, USA.
Virology. 2005 Jun 20;337(1):162-74. doi: 10.1016/j.virol.2005.03.035.
The major inducible 70-kDa heat shock protein (hsp72) binds measles virus (MV) nucleocapsids and increases MV gene expression. The cytoplasmic tail of the MV N protein (N(TAIL)) contains three hydrophobic domains (Box-1-3) that are potential targets of hsp72 interaction. Low affinity binding to Box-3 is correlated to hsp72-dependent stimulation of MV minireplicon reporter gene expression whereas interactions between hsp72 and Box-1 and/or -2 have not been documented. The present work showed that virus deficient in Box-3/hsp72 interaction retains the ability to form nucleocapsid/hsp72 complexes, identifying Box-2 but not Box-1 as a mediator of high affinity hsp72 binding. Box-2 is the binding site for the viral P protein X domain (XD), where P tethers the viral polymerase to nucleocapsid in support of transcription and genome replication, and competitive inhibition of XD binding to N(TAIL) by hsp72 was shown. Recognition of a common binding site by P and hsp72 represents a potential mechanism for host cell modulation of viral gene expression.
主要的诱导型70 kDa热休克蛋白（hsp72）与麻疹病毒（MV）核衣壳结合并增加MV基因表达。MV N蛋白的细胞质尾（N(TAIL)）包含三个疏水结构域（Box-1至3），它们是hsp72相互作用的潜在靶点。与Box-3的低亲和力结合与hsp72依赖的MV微型复制子报告基因表达刺激相关，而hsp72与Box-1和/或-2之间的相互作用尚未见报道。目前的研究表明，缺乏Box-3/hsp72相互作用的病毒保留了形成核衣壳/hsp72复合物的能力，确定Box-2而非Box-1是高亲和力hsp72结合的介质。Box-2是病毒P蛋白X结构域（XD）的结合位点，P在该位点将病毒聚合酶与核衣壳相连以支持转录和基因组复制，并且显示hsp72对XD与N(TAIL)结合具有竞争性抑制作用。P和hsp72对共同结合位点的识别代表了宿主细胞调节病毒基因表达的一种潜在机制。
