IMPLICATIONS OF ATOMIC-RESOLUTION STRUCTURES FOR CELL-ADHESION

Molecules involved in cell adhesion processes are often both structura lly and functionally modular, with subdomains that are members of larg e protein families. Recently, high-resolution structures have been det ermined for representative members of many of these families including fragments of integrins, cadherins, fibronectin-like domains, and immu noglobulin-like domains. These structures have enhanced our understand ing of cell adhesion processes at several levels. In almost all cases, ligand-binding sites have been visualized and provide insight into ho w these molecules mediate biologically important interactions. Metal-b inding sites have been identified and characterized, allowing assessme nt of the role of bound ions in cell adhesion processes. Many of these structures serve as templates for modeling homologous domains in othe r proteins or, when the structure of a fragment consisting of more tha n one domain is determined, the structure of multidomain arrays of hom ologous domains. Knowledge of atomic structure also allows rational de sign of drugs that either mimic or target specific binding sites. In m any cases, high-resolution structures have revealed unexpected relatio nships that pose questions about the evolutionary origin of specific d omains. This review briefly describes several recently determined stru ctures of cell adhesion molecules, summarizes some of the main results of each structure, and highlights common features of different system s.