7ZWH

VWF Tubules of D1D2 and D'D3A1 domains

Summary for 7ZWH

• Entry DOI: 10.2210/pdb7zwh/pdb
• EMDB information: 14998
• Descriptor: von Willebrand factor, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: helical, tubule, vwa1, a1 domain, a1, vwf, von willebrand factor, helical tubule, blood clotting
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 312515.35

Authors

Javitt, G.,Fass, D. (deposition date: 2022-05-19, release date: 2022-07-13, Last modification date: 2025-07-02)

Primary citation

Javitt, G.,Yeshaya, N.,Khmelnitsky, L.,Fass, D.
Assembly of von Willebrand factor tubules with in vivo helical parameters requires A1 domain insertion.
Blood, 140:2835-2843, 2022

PubMed Abstract: The von Willebrand factor (VWF) glycoprotein is stored in tubular form in Weibel-Palade bodies (WPBs) before secretion from endothelial cells into the bloodstream. The organization of VWF in the tubules promotes formation of covalently linked VWF polymers and enables orderly secretion without polymer tangling. Recent studies have described the high-resolution structure of helical tubular cores formed in vitro by the D1D2 and D'D3 amino-terminal protein segments of VWF. Here we show that formation of tubules with the helical geometry observed for VWF in intracellular WPBs requires also the VWA1 (A1) domain. We reconstituted VWF tubules from segments containing the A1 domain and discovered it to be inserted between helical turns of the tubule, altering helical parameters and explaining the increased robustness of tubule formation when A1 is present. The conclusion from this observation is that the A1 domain has a direct role in VWF assembly, along with its known activity in hemostasis after secretion.

PubMed: 36179246
DOI: 10.1182/blood.2022017153

Experimental method

ELECTRON MICROSCOPY (3.2 Å)