Assembly of the Ebola Virus Nucleoprotein from a Chaperoned VP35 Complex.
Assembly of the Ebola Virus Nucleoprotein from a Chaperoned VP35 Complex.
复制标题
DOI：
10.1016/j.celrep.2015.06.003
复制
发表时间：
2015-07-07
期刊：
影响因子：
8.8
通讯作者：
Saphire EO
中科院分区：
文献类型：
--
作者：
Kirchdoerfer RN;Abelson DM;Li S;Wood MR;Saphire EO
埃博拉病毒NP寡聚化成在病毒体核心处发现的螺旋丝，使病毒RNA基因组包埋，并充当病毒核衣壳内的其他病毒蛋白的支架。我们鉴定了磷蛋白同源物VP 35的一部分，其以高亲和力与新生NP结合并调节NP组装和病毒基因组结合。去除VP 35肽导致NP通过其N-末端寡聚化臂自组装。NP寡聚化可能导致NP N-和C-末端结构域之间的构象变化，促进RNA结合。这些功能数据由NP°-VP 35复合物的晶体结构在2.4 nm分辨率下补充。由这些结构阐明的NP和VP 35之间的相互作用在丝状病毒中是保守的，并为治疗干预提供了关键靶标。
Ebolavirus NP oligomerizes into helical filaments found at the core of the virion, encapsidates the viral RNA genome, and serves as a scaffold for additional viral proteins within the viral nucleocapsid. We identified a portion of the phosphoprotein homologue VP35 that binds with high affinity to nascent NP and regulates NP assembly and viral genome binding. Removal of the VP35 peptide leads to NP self-assembly via its N-terminal oligomerization arm. NP oligomerization likely causes a conformational change between the NP N- and C-terminal domains, facilitating RNA binding. These functional data are complemented by a crystal structure of the NP°-VP35 complex at 2.4 Å resolution. The interactions between NP and VP35 illuminated by these structures are conserved among filoviruses and provide key targets for therapeutic intervention.