7a6o

Crystal Structure of the Complex of the Recombinant Von Willebrand Factor AIM-A1 domain and VHH81 at 2.1 Angstrom resolution

spinqualitylabelsall models 7a6o, resolution 2.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7a6o is a 2 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.117Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function L8E853_HUMAN Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.[PIRNR:PIRNR002495] Publication Abstract from PubMed Von Willebrand factor (VWF) activates in response to shear flow to initiate hemostasis, while aberrant activation could lead to thrombosis. Above a critical shear force, the A1 domain of VWF becomes activated and captures platelets via the GPIb-IX complex. Here we show that the shear-responsive element controlling VWF activation resides in the discontinuous autoinhibitory module (AIM) flanking A1. Application of tensile force in a single-molecule setting induces cooperative unfolding of the AIM to expose A1. The AIM-unfolding force is lowered by truncating either N- or C-terminal AIM region, type 2B VWD mutations, or binding of a ristocetin-mimicking monoclonal antibody, all of which could activate A1. Furthermore, the AIM is mechanically stabilized by the nanobody that comprises caplacizumab, the only FDA-approved anti-thrombotic drug to-date that targets VWF. Thus, the AIM is a mechano-regulator of VWF activity. Its conformational dynamics may define the extent of VWF autoinhibition and subsequent activation under force. Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module.,Arce NA, Cao W, Brown AK, Legan ER, Wilson MS, Xu ER, Berndt MC, Emsley J, Zhang XF, Li R Nat Commun. 2021 Apr 21;12(1):2360. doi: 10.1038/s41467-021-22634-x. PMID:33883551 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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