Abstract

Integrins are major metazoan cell surface receptors that interact with extracellular matrix proteins. They are heterodimers of alpha and beta subunits that contain a large extracellular domain responsible for ligand binding, a single transmembrane domain and a cytoplasmic domain of 20-70 amino acid residues. Integrins play central roles in cell adhesion, cell migration and control of cell differentiation, proliferation and programmed cell death. A hallmark of the integrins is the ability of individual family members to recognize multiple ligands. Most integrins recognize relatively short peptide motifs such as RGD, LDV or DLXXL and, in general, a key constituent residue is an acidic amino acid. Some collagens have another - different - integrin binding motif. The ligand specificities rely on both subunits of a given alpha-beta heterodimer. Proteins that contain RGD attachment sites together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. RGD was originally identified as the sequence in fibronectin that engages the fibronectin receptor, integrin alpha 5 beta 1. RGD sequences have also been found to be responsible for the cell adhesive properties of a number of other proteins, including fibrinogen, von Willebrand factor and victronectin. Many snake venoms are rich in RGD peptides - a testament to the importance of the integrin system. While their motives may be more benign, the pharmaceutical industry also finds the integrin-RGD system to be of considerable interest. Antagonists could be effective for therapeutic intervention in e.g. cancer, thrombosis and numerous inflammatory conditions.