title: ADAMTS13 and von Willebrand factor interactions.
abstract: OBJECTIVE
  ADAMTS13 is a zinc-containing metalloprotease that cleaves von Willebrand factor (VWF). Deficiency of plasma ADAMTS13 activity is accountable for a potentially fatal blood disorder thrombotic thrombocytopenic purpura (TTP). Understanding of ADAMTS13-VWF interaction is essential for developing novel treatments to this disorder.
  
  
  RESULTS
  Despite the proteolytic activity of ADAMTS13 being restricted to the metalloprotease domain, the ancillary proximal C-terminal domains including the disintegrin domain, first TSP-1 repeat, cysteine-rich region, and spacer domain are all required for cleavage of VWF and its analogs. Recent studies have added to our understandings of the role of the specific regions in the disintegrin domain, the cysteine-rich domain, and the spacer domain responsible for its interaction with VWF. Additionally, regulative functions of the distal portion of ADAMTS13 including the TSP-1 2-8 repeats and the CUB domains have been proposed. Finally, fine mapping of anti-ADAMTS13 antibody epitopes have provided further insight into the essential structural elements in ADAMTS13 for VWF binding and the mechanism of autoantibody-mediated TTP.
  
  
  CONCLUSIONS
  Significant progress has been made in our understandings of the structure-function relationship of ADAMTS13 in the past decade. To further investigate ADAMTS13-VWF interactions for medical applications, these interactions must be studied under physiological conditions in vivo.
authors.affiliation: Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Zander
authors.forename: Wenjing
authors.initials: W
authors.lastname: Cao
authors.forename: X Long
authors.initials: XL
authors.lastname: Zheng
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D000071120:ADAMTS13 Protein; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D016056:Immunodominant Epitopes; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human