CD2 and the nature of protein interactions mediating cell-cell recognition
Davis SJ, Ikemizu S, Wild MK, van der Merwe PA. (1998), Immunol Rev. 163, 217-36
Rapid progress has recently been made in characterising the structures of leukocyte cell-surface molecules. Detailed analyses of the structure and interactions of CD2 were the first involving a molecule that has not been directly linked to antigen recognition in the manner of antigen receptors or co-receptors. It seems highly likely that the properties of ligand binding by CD2 are relevant to the general mechanisms of cell-cell recognition. As an example of biological recognition, the defining characteristic of cell-cell contact is that it involves the simultaneous interaction of hundreds, if not thousands, of molecules. Affinity and kinetic analyses of ligand binding by CD2 indicated that the protein interactions mediating cell-cell contact, whilst highly specific, are much weaker than initially anticipated, probably due to the requirement that such contacts be easily reversible. Simultaneously, in addressing the mechanism of this mode of recognition, structural and mutational studies focussed on the role of charged residues clustered in the ligand-binding face of CD2, yielding the concept that electrostatic complementarity, rather than surface-shape complementarity, is the dominant feature of specific, low-affinity protein recognition at the cell surface by CD2. The crystallographic analysis of the CD2-binding domain of CD58 strongly supports this concept.
Key figure: The structure of sCD2
In (A), two orthogonal views of a schematic diagram of the polypeptide fold of rat sCD2 are shown in an orientation in which the lipid bilayer is assumed to lie at the bottom of the illustration. The positions of the key structural elements, domain 1 (d1), linker (I), domain 2 (d2) and stalk (s) are indicated. All of the β-strands in the first view are labelled. In (B), α-carbon trace superpositions for CD2, CD4 domains 1 and 2 and the Fab NEW light chain are shown. The molecules are superimposed on domain 2 of CD2. CD2 is shown in red, CD4 in blue and the light chain in green. The images in A and B were drawn using the programme MOLSCRIPT (84).