3ZQK

Von Willebrand Factor A2 domain with calcium

Summary for 3ZQK

• Entry DOI: 10.2210/pdb3zqk/pdb
• Related: 1AO3 1ATZ 1AUQ 1FE8 1FNS 1IJB 1IJK 1M10 1OAK 1SQ0 1U0N 1UEX 2ADF
• Descriptor: VON WILLEBRAND FACTOR, GLYCEROL, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: blood clotting, adamts-13, force sensor, von willebrand disease, vwa domain, haemostasis
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P04275
• Total number of polymer chains: 3
• Total formula weight: 67414.74

Authors

Jakobi, A.J.,Huizinga, E.G. (deposition date: 2011-06-09, release date: 2011-07-27, Last modification date: 2024-10-09)

Primary citation

Jakobi, A.J.,Mashaghi, A.,Tans, S.J.,Huizinga, E.G.
Calcium Modulates Force Sensing by the Von Willebrand Factor A2 Domain.
Nat.Commun., 2:385-, 2011

PubMed Abstract: von Willebrand factor (VWF) multimers mediate primary adhesion and aggregation of platelets. VWF potency critically depends on multimer size, which is regulated by a feedback mechanism involving shear-induced unfolding of the VWF-A2 domain and cleavage by the metalloprotease ADAMTS-13. Here we report crystallographic and single-molecule optical tweezers data on VWF-A2 providing mechanistic insight into calcium-mediated stabilization of the native conformation that protects A2 from cleavage by ADAMTS-13. Unfolding of A2 requires higher forces when calcium is present and primarily proceeds through a mechanically stable intermediate with non-native calcium coordination. Calcium further accelerates refolding markedly, in particular, under applied load. We propose that calcium improves force sensing by allowing reversible force switching under physiologically relevant hydrodynamic conditions. Our data show for the first time the relevance of metal coordination for mechanical properties of a protein involved in mechanosensing.

PubMed: 21750539
DOI: 10.1038/NCOMMS1385

Experimental method

X-RAY DIFFRACTION (1.7 Å)