Premium
CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily structural motifs
Author(s) -
Kitadokoro Kengo,
Bordo Domenico,
Galli Giuliano,
Petracca Roberto,
Falugi Fabiana,
Abrignani Sergio,
Grandi Guido,
Bolognesi Martino
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.1.12
Subject(s) - cd81 , tetraspanin , biology , transmembrane domain , transmembrane protein , glycoprotein , protein subunit , protein structure , protein domain , microbiology and biotechnology , membrane protein , virus , biochemistry , genetics , hepatitis c virus , receptor , gene , cell , membrane
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 Å resolution. Each subunit within the homodimeric protein displays a mushroom‐like structure, composed of five α‐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 hetero‐dimers 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.