INTERACTION BETWEEN HUMAN CD2 AND CD58 INVOLVES THE MAJOR BETA-SHEET SURFACE OF EACH OF THEIR RESPECTIVE ADHESION DOMAINS

The CD58 binding site on human CD2 was recently shown by nuclear magne tic resonance structural data in conjunction with site-directed mutage nesis to be a highly charged surface area covering similar to 770 Angs trom(2) on the major AGFCC'C'' face of the CD2 immunoglobulin-like (Ig -like) NH2-terminal domain. Here we have identified the other binding surface of the CD2-CD58 adhesion pair by mutating charged residues sha red among CD2 ligands (human CD58, sheep CD58, and human CD48) that ar e predicted to be solvent exposed on a molecular model of the Ig-like adhesion domain of human CD58. This site includes beta strand residues along the C strand (E25, K29, and K30), in the middle of the C' stran d (E37) and in the G strand (K87). In addition, several residues on th e CC' loop (K32, D33, and K34) form this site. Thus, the interaction b etween CD2 and CD58 involves the major beta sheet surface of each adhe sion domain. Possible docking orientations for the CD2-CD58 molecular complex are offered. Strict conservation of human and sheep CD58 resid ues within the involved C and C' strands and CC' loop suggests that th is region is particularly important for stable formation of the CD2-CD 58 complex. The analysis of this complex offers molecular insight into the nature of a receptor-ligand pair involving two Ig family members.