Structure of an integrin-ligand complex deduced from solution x-ray scattering and site-directed mutagenesis.

The structural basis of the interaction of integrin heterodimers with their physiological ligands is poorly understood. We have used solution x-ray scattering to visualize the head region of integrin alpha 5 beta 1 in an inactive (Ca2+-occupied) state, and in complex with a fragment of fibronectin containing the RGD and synergy recognition sequences. Shape reconstructions of the data have been interpreted in terms of appropriate molecular models.

Mapping functional residues onto integrin crystal structures.

Historical data, available in the literature, concerning the sites responsible for integrin-ligand binding and activation may now be transposed onto recently solved crystal structures of integrin dimers and functional domains. The data were obtained through studies of natural and engineered mutations within integrins, and analyses of the epitopes for function-altering monoclonal antibodies. In the past two years, this combining of structure and function has led to the development of novel hypotheses for the mechanisms of integrin regulation.