Crystal structure of the CD2-binding domain of CD58 (lymphocyte function-associated antigen 3) at 1.8-angstrom resolution

The binding of the cell surface molecule CD58 (formerly lymphocyte function -associated antigen 3) to its ligand, CD2, significantly increases the sens itivity of antigen recognition by T cells. This was the first heterophilic cell adhesion interaction to be discovered and is now an important paradigm for analyzing the structural basis of cell-cell recognition. The crystal s tructure of a CD2-binding chimeric form of CD58, solved to 1.8-Angstrom res olution, reveals that the ligand binding domain of CD58 has the expected Ig superfamily V-set topology and shares several of the hitherto unique struc tural features of CD2, consistent with previous speculation that the genes encoding these molecules arose via duplication of a common precursor, Never theless, evidence for considerable divergence of CD2 and CD58 is also impli cit in the structures, Mutations that disrupt CD2 binding map to the highly acidic surface of the AGFCC'C " P-sheet of CD58, which, unexpectedly, lack s marked shape complementarity to the equivalent, rather more basic CD58-bi nding face of human CD2, The specificity of the very weak interactions of p roteins mediating cell-cell recognition may often derive largely from elect rostatic complementarity, with shape matching at the protein-protein interf ace being less exact than for interactions that combine specificity with hi gh affinity, such as those involving antibodies.