CRYSTAL-STRUCTURE OF THE EXTRACELLULAR REGION OF THE HUMAN CELL-ADHESION MOLECULE CD2 AT 2.5-ANGSTROM RESOLUTION

Background: The T-lymphocyte antigen CD2 is an adhesion molecule impli cated in immune responses in vivo. The extracellular regions of the hu man and rat homologues of CD2 share only 45 % sequence identity and bi nd different protein ligands. Comparison of the human and rat soluble CD2 (sCD2) structures should provide insights into the structural basi s of cell surface recognition. Results: We therefore determined the cr ystal structure of a form of human sCD2 with single N-acetylglucosamin e residues at each glycosylation site to 2.5 Angstrom resolution with an R-factor of 19.3 %. It is composed of two immunoglobulin superfamil y domains similar to those of rat sCD2, but the relative orientation o f the domains in the two homologues differs by up to 20 degrees. An in teraction involving the flat, highly charged, ligand binding GFCC'C'' faces of crystallographically related human sCD2 molecules duplicates, in a different lattice, that observed in the rat sCD2 crystals. Concl usions: Intramolecular flexibility appears to be a conserved feature o f CD2. The head-to-head interaction between molecules represents a gen eral model for interactions between adhesion molecules of this structu ral class. Ligand specificity may be influenced by the distribution of charged residues on the binding face.