The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding

Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10641-6. doi: 10.1073/pnas.162360499. Epub 2002 Jul 16.


Human complement receptor type 2 (CD21) is the cellular receptor for Epstein-Barr virus (EBV), a human tumor virus. The N-terminal two short consensus repeats (SCR1-SCR2) of the receptor interact with the EBV glycoprotein gp350/220 and also with the natural CD21 ligand C3d. Here we present the crystal structure of the CD21 SCR1-SCR2 fragment in the absence of ligand and demonstrate that it is able to bind EBV. Based on a functional analysis of wild-type and mutant CD21 and molecular modeling, we identify a likely region for EBV attachment and demonstrate that this region is not involved in the interaction with C3d. A comparison with the previously determined structure of CD21 SCR1-SCR2 in complex with C3d shows that, in both cases, CD21 assumes compact V-shaped conformations. However, our analysis reveals a surprising degree of flexibility at the SCR1-SCR2 interface, suggesting interactions between the two domains are not specific. We present evidence that the V-shaped conformation is induced by deglycosylation of the protein, and that physiologic glycosylation of CD21 would result in a more extended conformation, perhaps with additional epitopes for C3d binding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbohydrate Sequence
  • Complement C3d / chemistry*
  • Complement C3d / immunology
  • Crystallography, X-Ray
  • Herpesvirus 4, Human / chemistry*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Receptors, Complement 3d / chemistry*
  • Receptors, Complement 3d / genetics
  • Receptors, Complement 3d / immunology


  • Receptors, Complement 3d
  • Complement C3d

Associated data

  • PDB/1LY2