The 2.8 angstrom structure of a T=4 animal virus and its implications for membrane translocation of RNA
The 2.8 angstrom structure of a T=4 animal virus and its implications for membrane translocation of RNA
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DOI：
10.1006/jmbi.1996.0437
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发表时间：
1996-08-09
影响因子：
5.6
通讯作者：
Johnson, JE
中科院分区：
文献类型：
--
作者：
Munshi, S;Liljas, L;Johnson, JE
简单RNA动物病毒通常通过受体介导的内吞作用进入细胞，随后是酸性pH依赖性释放和RNA跨内体膜易位。T = 3诺达病毒含有预制的五聚体螺旋束，这些束通过装配依赖的自蛋白水解从亚基的其余部分切割出来，它们被定位为通过颗粒的5倍轴释放。我们之前提出这些束可能作为RNA膜易位的导管。对这一假设的进一步支持现在由T = 4 RNA病毒的第一个原子分辨率结构提供，我们发现切割位点和螺旋束与在T = 3诺达病毒中观察到的几乎相同。螺旋的长度足以跨越膜双分子层，螺旋束的内径可以容纳ssRNA。T = 4粒子的平均外径为410埃，由单一亚基类型的240个副本组成。该亚基由螺旋状内结构域（发生裂解的地方）组成，该结构域包含一个规范的、病毒的、形成连续壳的八链β -三明治的前后残基。在壳结构域的两条链之间插入133个具有免疫球蛋白c型折叠的残基。最初的基因产物由644个氨基酸残基组成，在本分析确定的成熟颗粒中被切割在Asn570和Phe571残基之间。(C) 1996学术出版社有限公司
Simple RNA animal viruses generally enter cells through receptor-mediated endocytosis followed by acid pH dependent release and translocation of RNA across the endosomal membrane. The T = 3 nodaviruses contain prefabricated pentameric helical bundles that are cleaved from the remainder of the subunits by an assembly-dependent auto-proteolysis and they are positioned for release through 5-fold axes of the particle. We previously proposed that these bundles may serve as conduits for RNA membrane translocation. Additional support for this hypothesis is now provided by the first atomic resolution structure of a T = 4 RNA virus, where we find cleavage sites and helical bundles nearly identical with those observed in T = 3 nodaviruses. The helices are of sufficient length to span a membrane bilayer and the internal diameter of the coiled bundle could accommodate ssRNA. The T = 4 particle has a mean outer diameter of 410 Angstrom and is formed by 240 copies of a single subunit type. The subunit is composed of a helical inner domain (where the cleavage occurs) containing residues preceding and following a canonical, viral, eight-stranded beta-sandwich that forms the contiguous shell. Inserted between two strands of the shell domain are 133 residues with an immunoglobulin c-type fold. The initial gene product consists of 644 amino acid residues and is cleaved between residues Asn570 and Phe571 in the mature particle determined in this analysis. (C) 1996 Academic Press Limited.