Structure and proteolytic properties of ADAMTS13, a metalloprotease involved in the pathogenesis of thrombotic microangiopathies.

摘要: ADAMTS13 is a 190-kDa zinc protease encoded by gene located on chromosome 9q34. This specifically hydrolyzes von Willebrand factor (VWF) multimers, thus causing VWF size reduction. belongs to the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS) family, involved in proteolytic processing of many matrix proteins. consists numerous domains, including metalloprotease domain, disintegrin several thrombospondin (TSP1) repeats, cysteine-rich spacer and two CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, Bone morphogenetic protein) domains. cleaves single peptide bond (Tyr(1605)-Met(1606)) central A2 domain molecule. cleavage essential reduce ultralarge polymers, which, when exposed high shear stress microcirculation, are prone form platelets clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs). In this chapter, we (a) discuss current knowledge structure-function aspects its involvement pathogenesis TMAs, (b) address ongoing controversies, (c) indicate direction future investigations.