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ADAMTS13 pp 39–57Cite as

ADAMTS13: Structure and Function

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Abstract

ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF), has been shown to have both antithrombotic and anti-inflammatory activities. Severe deficiency of plasma ADAMTS13 activity is a primary cause of thrombotic thrombocytopenic purpura (TTP), a potentially fatal syndrome, but mild to moderate deficiency of plasma ADAMTS13 activity may be associated with increased risk for many other pathologies, including myocardial/cerebral infarction, malignant malaria, preeclampsia, and acute and chronic inflammation. Structure–function analyses demonstrate that N-terminal fragment containing a metalloprotease domain, a disintegrin domain, the first thrombospondin type 1 repeat (TSP1 1), a cysteine-rich domain, and a spacer domain (i.e., MDTCS) appears to be sufficient for recognition and proteolytic cleavage of VWF in vitro and in vivo. The role of more distal C-terminal domains including TSP1 2–8 repeats and CUB (the complement C1r/C1s, Uegf, and Bmp1) domains remains to be determined. Recent studies suggest that TSP12–8 and CUB domains may negatively regulate ADAMTS13 activity. Further investigations of the binding sites of anti-ADAMTS13 autoantibodies from acquired TTP patients may help redesign ADAMTS13 protease for therapeutic use.

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Abbreviations

ADAMTS13:

A disintegrin and metalloprotease with thrombospondin type 1 repeats, 13

CUB:

For the complement C1r/C1s, Uegf, Bmp1

DTCS:

Disintegrin, first thrombospondin type 1 repeat, Cys-rich, and spacer domains

ELISA:

Enzyme-linked immunosorbent assay

HNPs:

Human neutrophil peptides

HSCs:

Hepatic stellate cells

K D :

Dissociation constant

MMPIs:

Matrix metalloprotease inhibitors

TTP:

Thrombotic thrombocytopenic purpura

ULVWF:

Ultra-large VWF

VWF:

von Willebrand factor

VWF73:

A VWF peptide containing 73 amino acids from D1596 to R1668

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Acknowledgment

The author thanks Ms. Hayley A. Hanby, a graduate student at the University of Pennsylvania, Philadelphia, PA, for her assistance in the initial draft of the manuscript.

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Correspondence to X. Long Zheng M.D., Ph.D. .

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Zheng, X.L. (2015). ADAMTS13: Structure and Function. In: Rodgers, G. (eds) ADAMTS13. Springer, Cham. https://doi.org/10.1007/978-3-319-08717-7_3

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