1U0N

The ternary von Willebrand Factor A1-glycoprotein Ibalpha-botrocetin complex

Summary for 1U0N

• Entry DOI: 10.2210/pdb1u0n/pdb
• Related: 1AUQ 1IJB 1IJK
• Descriptor: Von Willebrand factor, Botrocetin, Platelet glycoprotein Ib, ... (4 entities in total)
• Functional Keywords: rossmann fold, lrr motif, c-type lectin fold, protein-protein complex, blood clotting
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P04275 P22029 P22030; Membrane; Single-pass type I membrane protein: P07359
• Total number of polymer chains: 4
• Total formula weight: 83531.42

Authors

Fukuda, K.,Liddington, R.C. (deposition date: 2004-07-13, release date: 2005-04-19, Last modification date: 2024-10-30)

Primary citation

Fukuda, K.,Doggett, T.,Laurenzi, I.J.,Liddington, R.C.,Diacovo, T.G.
The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation
Nat.Struct.Mol.Biol., 12:152-159, 2005

PubMed Abstract: Botrocetin is a snake venom protein that enhances the affinity of the A1 domain of plasma von Willebrand factor (vWF) for the platelet receptor glycoprotein Ibalpha (GPIbalpha), an event that contributes to bleeding and host death. Here we describe a kinetic and crystallographic analysis of this interaction that reveals a novel mechanism of affinity enhancement. Using high-temporal-resolution microscopy, we show that botrocetin decreases the GPIbalpha off-rate two-fold in both human and mouse complexes without affecting the on-rate. The key to this behavior is that, upon binding of GPIbalpha to vWF-A1, botrocetin prebound to vWF-A1 makes no contacts initially with GPIbalpha, but subsequently slides around the A1 surface to form a new interface. This two-step mechanism and flexible coupling may prevent adverse alterations in on-rate of GPIbalpha for vWF-A1, and permit adaptation to structural differences in GPIbalpha and vWF in several prey species.

PubMed: 15665869
DOI: 10.1038/nsmb892

Experimental method

X-RAY DIFFRACTION (2.95 Å)