CD81 extracellular domain 3D structure: Insight into the tetraspanin superfamily structural motifs

Kengo Kitadokoro, Domenico Bordo, Giuliano Galli, Roberto Petracca, Fabiana Falugi, Sergio Abrignani, Guido Grandi, Martino Bolognesi

Research output: Contribution to journalArticlepeer-review


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 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.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalEMBO Journal
Issue number1-2
Publication statusPublished - Jan 15 2001


  • CD81 extracellular domain structure
  • HCV receptor
  • Human CD81
  • Tetraspan-web
  • Tetraspanins

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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