The Immunoglobulin Superfamily

Abstract

Publisher Summary This chapter discusses the immunoglobulin superfamily (IgSF) members involved in cell adhesion and/or recognition. The Ig fold has evolved and been employed to bind small ligands, such as growth factors (e.g., platelet derived growth factor, PDGF), stem cell factor (SCF), and vascular endothelial cell growth factor (VEGF). Some of the recent work mapping their binding sites, which tend to be discrete binding pockets in internal domains, is discussed in the chapter. The structural themes emerging from homophilic cell adhesion molecule (CAM) interactions are surprisingly diverse when compared with heterotypic modes. An early model for how homophilic binding may occur came from the work on gp80, the major adhesin expressed in the late multicellular phase of the slime mould Dictyosteliurn discoideum. The interaction of homophilic CAMs may be a two-part process. The first is in an initial alignment of apposed CAMs, most probably in an anti-parallel orientation with initial engagement of dominant interaction or recognition motifs in key domains. Secondly, this is followed by the docking of additional domains or dimerization of molecules in cis by membrane proximal domains that lead to stabilization of the homophilic interaction. The overall pattern of homophilic IgSF interactions that has emerged from recent studies points to a more complex mode than for heterophilic adhesion where dominant domains(s) are located in membrane distal N-terminal positions and interact head to head. Homophilic IgSF CAMs display a range of binding modes from the simple head-to-head interactions to more complex interdigitating interactions requiring correct alignments of the CAMs along their lengths.