Backbone resonance assignments of the A2 domain of mouse von Willebrand factor

Backbone resonance assignments of the A2 domain of mouse von Willebrand factor

von Willebrand factor (vWF) is an adhesive plasma protein that is important for platelet adhesion in normal hemostasis in response to vascular injury. Although large vWF multimers are released from storage granules of platelets and (sub-)endothelial cells in response to hemostatic stimuli, for norma...

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Published in:Biomolecular NMR assignments Vol. 15; no. 2; pp. 427 - 431
Main Authors: Morimoto, Daichi, Osugi, Masanori, Mahana, Yutaka, Walinda, Erik, Shirakawa, Masahiro, Sugase, Kenji
Format: Journal Article
Language:English
Published: Dordrecht Springer Netherlands 01-10-2021
Springer Nature B.V
Subjects:
Amino Acid Sequence
Animals
Biochemistry
Biological and Medical Physics
Biophysics
Crystal structure
Endothelial cells
Fluid flow
Hemostasis
Mechanical stimuli
Mice
NMR
Nuclear magnetic resonance
Nuclear Magnetic Resonance, Biomolecular
Physics
Physics and Astronomy
Platelets
Polymer Sciences
Protein Domains
Protein structure
Protein Structure, Secondary
Proteolysis
Secondary structure
Shear stress
Von Willebrand factor
von Willebrand Factor - chemistry
von Willebrand Factor - metabolism
Shear stress
von Willebrand disease
Thrombotic thrombocytopenic purpura
A2 domain
Hemostasis
von Willebrand factor
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Summary:von Willebrand factor (vWF) is an adhesive plasma protein that is important for platelet adhesion in normal hemostasis in response to vascular injury. Although large vWF multimers are released from storage granules of platelets and (sub-)endothelial cells in response to hemostatic stimuli, for normal physiological function, vWF multimers are required to be cleaved into smaller multimeric forms. The plasma metalloproteinase ADAMTS13 specifically cleaves the peptide bond located in the middle of the A2 domain of vWF (vWF-A2), but the cleavage site is buried inside the structure of vWF and is difficult to access in the absence of elevated flow shear stress. On the other hand, in the presence of high vascular shear stress, the structure of vWF-A2 is supposed to be unfolded, thereby becoming accessible for proteolysis by ADAMTS13. However, the atomic-level mechanism underlying shear-induced structural changes of vWF-A2 remains unclear and to date no solution NMR information is available. In this study, we present the backbone 1 H, 13 C, and 15 N resonance assignments of mouse vWF-A2; side chain assignments of 13 C β are also provided. Secondary structure propensity analysis based on the assigned chemical shifts showed that mouse vWF-A2 forms similar secondary structures in solution to the previously determined crystal structure of human vWF-A2. The obtained NMR assignment data will contribute to an atomic-level characterization of shear-induced unfolding of vWF-A2 in solution.
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ISSN:1874-2718
1874-270X
1874-270X
DOI:10.1007/s12104-021-10041-8