Structural biology of the cell adhesion protein CD2: alternatively folded states and structure-function relation

Abstract

Cluster of differentiation 2 (CD2) is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells and plays an important role in mediating cell adhesion in both T-lymphocytes and in signal transduction. The understanding of the biochemical basis of molecular recognition by the cell adhesion molecule CD2 has been advanced greatly through the determination of structures and the dynamic properties of the complexes and their individual components and through site-directed mutagenesis. A number of general principles can be derived from the structural and functional studies of the extracellular domains of CD2 and CD58 and their complex. Significant electrostatic interactions within the protein-protein interfaces contribute directly to the formation of macromolecular complexes of CD2 and CD58. Also, residues located on the protein-protein interface demonstrate a certain degree of conformational change upon the formation of a complex. Structural analysis of CD2 has revealed that this adhesion molecule exhibits strong conformational flexibility with a partial non-native helical conformation at high temperatures and in the presence of an organic solvent. In addition, it can be converted into a domain swapped dimer, or trimer and tetramer through hinge deletion. Thus, the conformational status of the adhesive proteins contributes to the regulation of cell adhesion and the folding of CD2.