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Proc Natl Acad Sci U S A
2014 Dec 30;11152:18584-9. doi: 10.1073/pnas.1413282112.
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Allosteric activation of ADAMTS13 by von Willebrand factor.
Muia J
,
Zhu J
,
Gupta G
,
Haberichter SL
,
Friedman KD
,
Feys HB
,
Deforche L
,
Vanhoorelbeke K
,
Westfield LA
,
Roth R
,
Tolia NH
,
Heuser JE
,
Sadler JE
.
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The metalloprotease ADAMTS13 cleaves von Willebrand factor (VWF) within endovascular platelet aggregates, and ADAMTS13 deficiency causes fatal microvascular thrombosis. The proximal metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains of ADAMTS13 recognize a cryptic site in VWF that is exposed by tensile force. Another seven T and two complement C1r/C1s, sea urchin epidermal growth factor, and bone morphogenetic protein (CUB) domains of uncertain function are C-terminal to the MDTCS domains. We find that the distal T8-CUB2 domains markedly inhibit substrate cleavage, and binding of VWF or monoclonal antibodies to distal ADAMTS13 domains relieves this autoinhibition. Small angle X-ray scattering data indicate that distal T-CUB domains interact with proximal MDTCS domains. Thus, ADAMTS13 is regulated by substrate-induced allosteric activation, which may optimize VWF cleavage under fluid shear stress in vivo. Distal domains of other ADAMTS proteases may have similar allosteric properties.
Akiyama,
Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor.
2009, Pubmed
Akiyama,
Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor.
2009,
Pubmed
Anderson,
Zinc and calcium ions cooperatively modulate ADAMTS13 activity.
2006,
Pubmed
Andersson,
High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women.
2012,
Pubmed
Apte,
A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms.
2009,
Pubmed
Banno,
Identification of strain-specific variants of mouse Adamts13 gene encoding von Willebrand factor-cleaving protease.
2004,
Pubmed
Banno,
The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation.
2009,
Pubmed
Bohne-Lang,
GlyProt: in silico glycosylation of proteins.
2005,
Pubmed
Bongers,
Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients.
2009,
Pubmed
Crawley,
Proteolytic inactivation of ADAMTS13 by thrombin and plasmin.
2005,
Pubmed
Crawley,
Evidence that high von Willebrand factor and low ADAMTS-13 levels independently increase the risk of a non-fatal heart attack.
2008,
Pubmed
Di Stasio,
Mechanistic studies on ADAMTS13 catalysis.
2008,
Pubmed
Feys,
Multi-step binding of ADAMTS-13 to von Willebrand factor.
2009,
Pubmed
Feys,
Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus).
2010,
Pubmed
Feys,
ADAMTS-13 plasma level determination uncovers antigen absence in acquired thrombotic thrombocytopenic purpura and ethnic differences.
2006,
Pubmed
Franke,
DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering.
2009,
Pubmed
Fujikawa,
Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family.
2001,
Pubmed
Furlan,
Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis.
1996,
Pubmed
Furlan,
von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.
1998,
Pubmed
Gandhi,
ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice.
2012,
Pubmed
Gao,
Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity.
2008,
Pubmed
Gao,
Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease.
2006,
Pubmed
Gerritsen,
Partial amino acid sequence of purified von Willebrand factor-cleaving protease.
2001,
Pubmed
Ginsburg,
Molecular genetics of von Willebrand disease.
1992,
Pubmed
Girma,
Limited proteolysis of human von Willebrand factor by Staphylococcus aureus V-8 protease: isolation and partial characterization of a platelet-binding domain.
1986,
Pubmed
Hassenpflug,
Impact of mutations in the von Willebrand factor A2 domain on ADAMTS13-dependent proteolysis.
2006,
Pubmed
Heuser,
Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release.
1979,
Pubmed
Heuser,
Protocol for 3-D visualization of molecules on mica via the quick-freeze, deep-etch technique.
1989,
Pubmed
Heuser,
Procedure for freeze-drying molecules adsorbed to mica flakes.
1983,
Pubmed
Hiura,
Proteolytic fragmentation and sugar chains of plasma ADAMTS13 purified by a conformation-dependent monoclonal antibody.
2010,
Pubmed
Hubmacher,
Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function.
2011,
Pubmed
Hura,
Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS).
2009,
Pubmed
Kokame,
FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay.
2005,
Pubmed
Le Goff,
The ADAMTS(L) family and human genetic disorders.
2011,
Pubmed
Levy,
Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura.
2001,
Pubmed
Majerus,
Binding of ADAMTS13 to von Willebrand factor.
2005,
Pubmed
Mosyak,
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5.
2008,
Pubmed
Muia,
An optimized fluorogenic ADAMTS13 assay with increased sensitivity for the investigation of patients with thrombotic thrombocytopenic purpura.
2013,
Pubmed
Nichols,
von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA).
2008,
Pubmed
Rauch,
Antibody-based prevention of von Willebrand factor degradation mediated by circulatory assist devices.
2014,
Pubmed
Shi,
Latent TGF-β structure and activation.
2011,
Pubmed
Soejima,
A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease?
2001,
Pubmed
Suarez,
Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices.
2011,
Pubmed
Svergun,
Restoring low resolution structure of biological macromolecules from solution scattering using simulated annealing.
1999,
Pubmed
Söding,
The HHpred interactive server for protein homology detection and structure prediction.
2005,
Pubmed
Tsai,
Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura.
1998,
Pubmed
Tsai,
Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion.
1996,
Pubmed
Wells,
Additivity of mutational effects in proteins.
1990,
Pubmed
Zanardelli,
A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF.
2009,
Pubmed
Zanardelli,
ADAMTS13 substrate recognition of von Willebrand factor A2 domain.
2006,
Pubmed
Zhang,
Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor.
2009,
Pubmed
Zhang,
The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow.
2007,
Pubmed
Zheng,
Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura.
2001,
Pubmed
Zhou,
An IAP retrotransposon in the mouse ADAMTS13 gene creates ADAMTS13 variant proteins that are less effective in cleaving von Willebrand factor multimers.
2007,
Pubmed
