1IJK

The von Willebrand Factor mutant (I546V) A1 domain-botrocetin Complex

Summary for 1IJK

• Entry DOI: 10.2210/pdb1ijk/pdb
• Related: 1AUQ 1IJB
• Descriptor: von Willebrand factor, Botrocetin, ... (4 entities in total)
• Functional Keywords: dinucleotide-binding fold, c-type lectin fold, blood clotting-toxin complex, blood clotting/toxin
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P04275 P22029 P22030
• Total number of polymer chains: 3
• Total formula weight: 53409.67

Authors

Fukuda, K.,Doggett, T.A.,Bankston, L.A.,Cruz, M.A.,Diacovo, T.G.,Liddington, R.C. (deposition date: 2001-04-26, release date: 2002-07-10, Last modification date: 2024-11-06)

Primary citation

Fukuda, K.,Doggett, T.A.,Bankston, L.A.,Cruz, M.A.,Diacovo, T.G.,Liddington, R.C.
Structural basis of von Willebrand factor activation by the snake toxin botrocetin.
Structure, 10:943-950, 2002

PubMed Abstract: The A1 domain of von Willebrand factor (vWF) mediates platelet adhesion to sites of vascular injury by binding to the platelet receptor glycoprotein Ib (GpIb), an interaction that is regulated by hydrodynamic shear forces. The GpIb binding surface of A1 is distinct from a regulatory region, suggesting that ligand binding is controlled allosterically. Here we report the crystal structures of the "gain-of-function" mutant A1 domain (I546V) and its complex with the exogenous activator botrocetin. We show that botrocetin switches the mutant A1 back toward the wild-type conformation, suggesting that affinity is enhanced by augmenting the GpIb binding surface rather than through allosteric control. Functional studies of platelet adhesion under flow further suggest that the activation mechanism is distinct from that of the gain-of-function mutation.

PubMed: 12121649
DOI: 10.1016/S0969-2126(02)00787-6

Experimental method

X-RAY DIFFRACTION (2.6 Å)