PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

Blog Article

ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.This protease specifically hydrolyzes von Willebrand factor (VWF) multimers, thus causing VWF size reduction.ADAMTS13 belongs to Jackets the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS) family, involved in proteolytic processing of many matrix proteins.ADAMTS13 consists of numerous domains including a metalloprotease domain, a disintegrin domain, several thrombospondin type 1 (TSP1) repeats, a cysteine-rich domain, a spacer domain and 2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone morphogenetic protein) domains.ADAMTS13 cleaves a single peptide bond (Tyr1605-Met1606) in the central A2 domain of the VWF molecule.

This proteolytic cleavage is essential to reduce the size of ultra-large VWF polymers, which, when exposed to high shear stress in the microcirculation, are prone to form with platelets clumps, which cause severe syndromes called thrombotic Hayward Saline C Parts microangiopathies (TMAs).In this review, we a) discuss the current knowledge of structure-function aspects of ADAMTS13 and its involvement in the pathogenesis of TMAs, b) address the recent findings concerning proteolytic processing of VWF multimers by different proteases, such as the leukocyte-derived serine and metallo-proteases and c) indicate the direction of future investigations.