Integrins: a review of their structure and mechanisms of ligand binding.

Adhesive interactions between cells and between cells and extracellular matrices play key roles in determining spatiotemporal positioning, influencing site-specific gene expression, and dictating proliferation rate. In addition, aberrant adhesion contributes to various aspects of disease pathology. These phenotypic effects of adhesion are mediated initially by the recognition of adhesive components of the extracellular matrix by membrane-intercalated receptor molecules and ultimately by the transduction of chemical and physical signals to the cell interior. Cell-cell and cell-matrix interactions are highly complex, since they involve the interfacing of surface membrane structures with each other or with three-dimensional aggregates of glycoproteins and proteoglycans, and it is this complexity that provides the necessary versatility for cells to react appropriately to either gross or subtle changes in their environment. Reagents with the ability to modulate adhesion could have many types of use: They could be employed to dissect the role of cell migration in development, provide insight into how adhesion might regulate gene expression and cell phenotype, and they could have widespread therapeutic applications in the treatment of thrombosis, inflammation and cancer. The quest to develop such reagents has necessitated the elucidation of the mechanisms of cell adhesion, and in particular the identification of the molecules involved and their modes of interaction. This article reviews the state of this quest; in particular, the molecular basis of ligand binding by integrin receptors.