Structural characterization of CD81-Claudin-1 hepatitis C virus receptor complexes
Structural characterization of CD81-Claudin-1 hepatitis C virus receptor complexes
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DOI：
10.1042/bst0390537
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发表时间：
2011-04-01
影响因子：
3.9
通讯作者：
Bill, Roslyn M.
中科院分区：
文献类型：
--
作者：
Bonander, Nicklas;Jamshad, Mohammed;Bill, Roslyn M.
四跨膜蛋白被认为通过协调相关分子的横向运动和运输进入四跨膜蛋白富集的微结构域来发挥其生物学功能。第二个四-TM（跨膜）结构域蛋白家族，Claudin超家族，是细胞紧密连接（紧密连接）的主要结构组分。虽然Claudin家族显示低序列同源性，似乎是从四跨膜蛋白进化不同，CD 81和Claudin-1是定义HCV（丙型肝炎病毒）进入的关键分子，我们最近证明，CD 81-Claudin-1复合物在这个过程中有一个重要的作用。为了理解CD 81-紧密连接蛋白-1复合物形成的分子基础，我们在去污剂和脂质环境中产生并纯化毫克量的全长CD 81和紧密连接蛋白-1（单独和复合）。这些纯化蛋白的结构表征将使我们能够定义病毒-细胞相互作用的潜在机制，并有助于设计针对病毒生命周期早期步骤的治疗剂。
Tetraspanins are thought to exert their biological function(s) by co-ordinating the lateral movement and trafficking of associated molecules into tetraspanin-enriched microdomains. A second four-TM (transmembrane) domain protein family, the Claudin superfamily, is the major structural component of cellular TJs (tight junctions). Although the Claudin family displays low sequence homology and appears to be evolutionarily distinct from the tetraspanins, CD81 and Claudin-1 are critical molecules defining HCV (hepatitis C virus) entry; we recently demonstrated that CD81-Claudin-1 complexes have an essential role in this process. To understand the molecular basis of CD81-Claudin-1 complex formation, we produced and purified milligram quantities of full-length CD81 and Claudin-1, alone and in complex, in both detergent and lipid contexts. Structural characterization of these purified proteins will allow us to define the mechanism(s) underlying virus-cell interactions and aid the design of therapeutic agents targeting early steps in the viral life cycle.