Structure-Activity Relationship Studies on ADAM Protein-Integrin Interactions
X. Lu, D. Lu, M. F. Scully and V. V. Kakkar
Affiliation: Thrombosis Research Institute, Manresa Road, London, SW3 6LR, UK.
The ADAM (a disintegrin and metalloprotease) family of proteins possess multi-domain structures composed of a signal peptide, a prodomain, a metalloprotease domain, a disintegrin-like domain, a cysteine rich domain, an epidermal growth factor-like domain, a transmembrane domain and cytoplasmic tail. The disintegrin-like domain shares sequence similarity with the soluble venom disintegrins, a family of proteins which are potent inhibitors of integrinmediated platelet aggregation and cell adhesion. Several ADAMs have been reported to interact with integrins, and the disintegrin-like domain may be crucial part in this respect. A description of structure-activity relationship of ADAM proteins interacting with integrin is outlined in this review. The review highlights recent reports on potential integrin family for ADAMs and how ADAMs selectively modulate interaction for integrin mediated cell function. Lastly, it describes progress in understanding the structural features and functional roles of the ADAMs in normal and pathological conditions and how this insight may assist the development of new therapeutic approaches.
Keywords: ADAM-15, RGD-disintegrin domain, metalloprotease domain, EGF-like domains, cytosolic portion
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