Journal Article

The Crystal Structure of Human CD21: Implications for Epstein-Barr Virus and C3d Binding

Fingeroth, Joyce D., Prota, Andrea E., Stehle, Thilo, Sage, David R.

2002

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Binding sites / Biological Sciences / Carbohydrate Sequence / Cell lines / Cellular biology / Complement C3d - chemistry / Complement C3d - immunology / Crystal structure / Crystallography, X-Ray / Epstein Barr virus infections / Epstein-Barr virus / Herpesvirus 4, Human - chemistry / Herpesvirus 4, Human - immunology / Humans / L cells / Ligands / Medical research / Models, Molecular / Molecular Sequence Data / Molecules / Polysaccharides / Proteins / Receptors, Complement 3d - chemistry / Receptors, Complement 3d - genetics / Receptors, Complement 3d - immunology / Tumors / Viruses