The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding.
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.
Harvard Medical School, Division of Experimental Medicine and Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115, USA.
Andrea E
AE
Prota
David R
DR
Sage
Thilo
T
Stehle
Joyce D
JD
Fingeroth
D002240:Carbohydrate Sequence; D015933:Complement C3d / Q000737:chemistry* / Q000276:immunology; D018360:Crystallography, X-Ray; D004854:Herpesvirus 4, Human / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017464:Receptors, Complement 3d / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D017464:Receptors, Complement 3d; D015933:Complement C3d