Author(s): Bajorath J, Metzler WJ, Linsley PS
Abstract Share this page
Abstract CD28/CD152-CD80/CD86 receptor-ligand interactions result in costimulatory signals critical for optimal T cell activation. CD28/CD152 and CD80/CD86 are members of the immunoglobulin superfamily (IgSF). Despite common receptor-ligand interactions, both receptor and ligand pairs share only limited sequence identity. A detailed molecular model of the extracellular Ig-like domain of human CD28 was constructed using a combination of different modeling methods. The model was based on the solution structure of CD152 and sequence comparison of the CD28/CD152 family. Assessment of the model revealed good stereochemical quality and sequence-structure compatibility. The CD28 model was used to map surface residues, N-linked glycosylation sites, and to compare residue conservation in CD28 and CD152. The location of N-linked glycosylation sites in CD28/CD152 restricts the surface area available for binding. Rigorous sequence conservation in CD28 and CD152 is limited to core IgSF consensus positions and surface residues implicated in ligand binding. Other surface residues vary greatly in CD28/CD152. Residues critical for ligand binding are surrounded by surface patches conserved only in either CD28 or CD152.
This article was published in J Mol Graph Model
and referenced in Journal of Multiple Sclerosis