CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily structural motifs
CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily structural motifs
复制标题
DOI：
10.1093/emboj/20.1.12
复制
发表时间：
2001-01-15
期刊：
影响因子：
11.4
通讯作者：
Bolognesi, M
中科院分区：
文献类型：
--
作者：
Kitadokoro, K;Bordo, D;Bolognesi, M
人CD81是丙型肝炎病毒包膜E2糖蛋白的已知受体，是一种属于四跨膜蛋白家族的跨膜蛋白。本文报道了人CD81大胞外结构域的晶体结构，分辨率为1.6埃。同源二聚体蛋白中的每个亚基都呈现出蘑菇状结构，由排列在“茎”和“头”亚结构域中的五个α -螺旋组成。已知与病毒结合有关的残基可定位在“头”亚结构域上，为抗病毒药物和疫苗的设计提供了基础。对160种四跨膜蛋白的序列分析表明，在CD81大胞外结构域中观察到的关键结构特征和新的蛋白质折叠在该家族中是保守的。基于这些，有人提出四跨膜蛋白可能通过位于“茎”亚结构域的保守疏水界面在细胞表面组装成同源和/或异源二聚体，同时通过“头”亚结构域与其他配体蛋白（包括丙型肝炎病毒E2）相互作用。这种相互作用的拓扑结构为所谓的四跨膜蛋白网络的组装提供了理论依据。
Human CD81, a known receptor for hepatitis C virus envelope E2 glycoprotein, is a transmembrane protein belonging to the tetraspanin family, The crystal structure of human CD81 large extracellular domain is reported here at 1.6 Angstrom resolution. Each subunit within the homodimeric protein displays a mushroom-like structure, composed of five alpha -helices arranged in 'stalk' and 'head' subdomains, Residues known to be involved in virus binding can be mapped onto the head subdomain, providing a basis for the design of antiviral drugs and vaccines. Sequence analysis of 160 tetraspanins indicates that key structural features and the new protein fold observed in the CD81 large extracellular domain are conserved within the family. On these bases, it is proposed that tetraspanins may assemble at the cell surface into homo- and/or heterodimers through a conserved hydrophobic interface located in the stalk subdomain, while interacting with other liganding proteins, including hepatitis C virus E2, through the head subdomain. The topology of such interactions provides a rationale for the assembly of the so-called tetraspan-web.