Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
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Journal
IF	>30 >20 >10 >5 all

Title	Structural basis of von Willebrand factor multimerization and tubular storage.
Journal, issue, pages	Blood, Vol. 139, Issue 22, Page 3314-3324, Year 2022
Publish date	Jun 2, 2022
Authors	Jianwei Zeng / Zimei Shu / Qian Liang / Jing Zhang / Wenman Wu / Xuefeng Wang / Aiwu Zhou /
PubMed Abstract	The von Willebrand factor (VWF) propeptide (domains D1D2) is essential for the assembly of VWF multimers and its tubular storage in Weibel-Palade bodies. However, detailed molecular mechanism ...The von Willebrand factor (VWF) propeptide (domains D1D2) is essential for the assembly of VWF multimers and its tubular storage in Weibel-Palade bodies. However, detailed molecular mechanism underlying this propeptide dependence is unclear. Here, we prepared Weibel-Palade body-like tubules using the N-terminal fragment of VWF and solved the cryo-electron microscopy structures of the tubule at atomic resolution. Detailed structural and biochemical analysis indicate that the propeptide forms a homodimer at acidic pH through the D2:D2 binding interface and then recruits 2 D'D3 domains, forming an intertwined D1D2D'D3 homodimer in essence. Stacking of these homodimers by the intermolecular D1:D2 interfaces brings 2 D3 domains face-to-face and facilitates their disulfide linkages and multimerization of VWF. Sequential stacking of these homodimers leads to a right-hand helical tubule for VWF storage. The clinically identified VWF mutations in the propeptide disrupted different steps of the assembling process, leading to diminished VWF multimers in von Willebrand diseases (VWD). Overall, these results indicate that the propeptide serves as a pH-sensing template for VWF multimerization and tubular storage. This sheds light on delivering normal propeptide as a template to rectify the defects in multimerization of VWD mutants.
External links	Blood / PubMed:35148377 / PubMed Central
Methods	EM (single particle)
Resolution	2.85 - 11.4 Å
Structure data	32687 7wpp EMDB-32687, PDB-7wpp: Cryo-EM structure of VWF D'D3 dimer complexed with D1D2 at 2.85 angstron resolution (1 unit) Method: EM (single particle) / Resolution: 2.85 Å 32688 7wpq EMDB-32688, PDB-7wpq: Cryo-EM structure of VWF D'D3 dimer complexed with D1D2 at 3.27 angstron resolution (2 units) Method: EM (single particle) / Resolution: 3.267 Å 32689 7wpr EMDB-32689, PDB-7wpr: VWF D'D3 dimer complexed with D1D2 at 4.39 angstron resolution(VWF tube) Method: EM (single particle) / Resolution: 4.39 Å 32690 7wps EMDB-32690, PDB-7wps: Cryo-EM structure of VWF D'D3 dimer complexed with D1D2 at 4.3 angstron resolution (7 units) Method: EM (single particle) / Resolution: 4.32 Å EMDB-32691: Cryo-EM structure of VWF D1D2 dimer Method: EM (single particle) / Resolution: 11.4 Å EMDB-32692: Cryo-EM structure of VWF D'D3 dimer Method: EM (single particle) / Resolution: 5.8 Å 32713 7wqt EMDB-32713, PDB-7wqt: Cryo-EM structure of VWF D'D3 dimer complexed with D1D2 at 4.3 angstron resolution (VWF tube) Method: EM (single particle) / Resolution: 4.3 Å
Chemicals	ChemComp-CA: Unknown entry ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine
Source	homo sapiens (human)
Keywords	BLOOD CLOTTING / blood / VWF / von Willebrand factor / von Willebrand disease / blood coagulation / multimer assembly / VWF assembly / D'D3 domain / D1D2 domain / D'D3 dimer / D1D2 Dimer / VWF Tube / repeating unit