1u0o

From Proteopedia

The mouse von Willebrand Factor A1-botrocetin complex

Overview

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.

About this Structure

1U0O is a Protein complex structure of sequences from Bothrops jararaca and Mus musculus. Full crystallographic information is available from OCA.

Reference

The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation., Fukuda K, Doggett T, Laurenzi IJ, Liddington RC, Diacovo TG, Nat Struct Mol Biol. 2005 Feb;12(2):152-9. Epub 2005 Jan 16. PMID:15665869

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