Mechanistic Features of Cell-Surface Adhesion Receptors

Biology depends on a vast array of information processing activities that are coordinated by diverse cell-surface adhesion receptors and their cognate ligands. Though these receptor–ligand pairs differ in chemical and structural terms, there are common principles that must be carefully considered in order to construct viable molecular and atomic mechanisms for signaling. This chapter examines the diversity of mechanisms thought to be involved in adhesion and signaling and highlights some of the shared principles that must be considered for all signaling pathways utilizing cell-surface receptors. The engagement of receptor–ligand pairs leads to an increase in their local density/concentration at cell–cell and cell–ECM interfaces, and in many cases may support a natural coupling between signaling and adhesive function. The chapter provides the quantitative understanding of both the cell–surface oligomeric state and the available concentration of receptor and ligand on their cell surfaces, as they dictate the relative stoichiometries and the type of signaling complexes that can be formed at cell–cell and cell–ECM interfaces. While direct structural information, in the form of X-ray and nuclear magnetic resonance (NMR) structures, may provide enormous insights into function and mechanism, in the absence of confirmatory biochemical data great care should be exercised in extrapolating intermolecular contacts observed in crystal structures to physiologically relevant protein–protein interfaces.