8D3C

VWF tubule derived from monomeric D1-A1

This is a non-PDB format compatible entry.

Summary for 8D3C

• Entry DOI: 10.2210/pdb8d3c/pdb
• EMDB information: 27156
• Descriptor: von Willebrand factor, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: vwf, tubule, blood clotting
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 16
• Total formula weight: 2616436.13

Authors

Anderson, J.R.,Li, J.,Springer, T.A.,Brown, A. (deposition date: 2022-06-01, release date: 2022-07-06, Last modification date: 2024-10-23)

Primary citation

Anderson, J.R.,Li, J.,Springer, T.A.,Brown, A.
Structures of VWF tubules before and after concatemerization reveal a mechanism of disulfide bond exchange.
Blood, 140:1419-1430, 2022

PubMed Abstract: von Willebrand factor (VWF) is an adhesive glycoprotein that circulates in the blood as disulfide-linked concatemers and functions in primary hemostasis. The loss of long VWF concatemers is associated with the excessive bleeding of type 2A von Willebrand disease (VWD). Formation of the disulfide bonds that concatemerize VWF requires VWF to self-associate into helical tubules, yet how the helical tubules template intermolecular disulfide bonds is not known. Here, we report electron cryomicroscopy (cryo-EM) structures of VWF tubules before and after intermolecular disulfide bond formation. The structures provide evidence that VWF tubulates through a charge-neutralization mechanism and that the A1 domain enhances tubule length by crosslinking successive helical turns. In addition, the structures reveal disulfide states before and after disulfide bond-mediated concatemerization. The structures and proposed assembly mechanism provide a foundation to rationalize VWD-causing mutations.

PubMed: 35776905
DOI: 10.1182/blood.2022016467

Experimental method

ELECTRON MICROSCOPY (3.1 Å)