Implications of atomic-resolution structures for cell adhesion.
Molecules involved in cell adhesion processes are often both structurally and functionally modular, with subdomains that are members of large protein families. Recently, high-resolution structures have been determined for representative members of many of these families including fragments of integrins, cadherins, fibronectin-like domains, and immunoglobulin-like domains. These structures have enhanced our understanding of cell adhesion processes at several levels. In almost all cases, ligand-binding sites have been visualized and provide insight into how these molecules mediate biologically important interactions. Metal-binding sites have been identified and characterized, allowing assessment of the role of bound ions in cell adhesion processes. Many of these structures serve as templates for modeling homologous domains in other proteins or, when the structure of a fragment consisting of more than one domain is determined, the structure of multidomain arrays of homologous domains. Knowledge of atomic structure also allows rational design of drugs that either mimic or target specific binding sites. In many cases, high-resolution structures have revealed unexpected relationships that pose questions about the evolutionary origin of specific domains. This review briefly describes several recently determined structures of cell adhesion molecules, summarizes some of the main results of each structure, and highlights common features of different systems.
Leahy
D J
DJ
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. leahy@groucho.med.jhmi.edu
D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D016023:Integrins / Q000737:chemistry
D015820:Cadherins; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D007136:Immunoglobulins; D016023:Integrins