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Recombinant CUB-1 domain polypeptide inhibits the cleavage of ULVWF strings by ADAMTS13 under flow conditions
- Source :
- Blood. 106:4139-4145
- Publication Year :
- 2005
- Publisher :
- American Society of Hematology, 2005.
-
Abstract
- The metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motif) converts the hyperreactive unusually large (UL) forms of von Willebrand factor (VWF) that are newly released from endothelial cells into less active plasma forms by cleaving a peptide bond in the VWF A2 domain. Familial or acquired deficiency of this metalloprotease is associated with thrombotic thrombocytopenic purpura (TTP). ADAMTS13 belongs to the ADAMTS metalloprotease family, but, unlike other members, it also contains 2 C-terminal CUB domains (complement component Clr/Cls, Uegf, and bone morphogenic protein 1). Mutations in the CUB region have been found in congenital TTP, but deletion of the region did not impair enzyme activity in conventional in vitro assays. We investigated the functions of the CUB domain in ADAMTS13 activity under flow conditions. We found that recombinant CUB-1 and CUB-1+2 polypeptides and synthetic peptides derived from CUB-1 partially blocked the cleavage of ULVWF by ADAMTS13 on the surface of endothelial cells under flow. The polypeptide bound immobilized and soluble forms of ULVWF, and blocked the adhesion of ADAMTS13-coated beads to immobilized ULVWF under flow. These results suggest that the CUB-1 domain may serve as the docking site for ADAMTS13 to bind ULVWF under flow, a critical step to initiate ULVWF proteolysis.
- Subjects :
- Adult
Male
Models, Molecular
Molecular Sequence Data
Immunology
ADAMTS13 Protein
Plasma protein binding
Hemostasis, Thrombosis, and Vascular Biology
Biochemistry
Protein structure
hemic and lymphatic diseases
von Willebrand Factor
Disintegrin
Humans
Amino Acid Sequence
Binding site
Cells, Cultured
Binding Sites
biology
Chemistry
ADAMTS
fungi
Cell Biology
Hematology
Middle Aged
CUB domain
Molecular biology
ADAM Proteins
Recombinant Proteins
ADAMTS13
Protein Structure, Tertiary
Molecular Weight
Chromatography, Gel
biology.protein
Female
Peptides
Sequence Alignment
Protein Binding
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....46b2570a5981fd94ad0ebb289252e990
- Full Text :
- https://doi.org/10.1182/blood-2005-05-2029