1u0n

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{{STRUCTURE_1u0n| PDB=1u0n | SCENE= }}
{{STRUCTURE_1u0n| PDB=1u0n | SCENE= }}
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'''The ternary von Willebrand Factor A1-glycoprotein Ibalpha-botrocetin complex'''
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===The ternary von Willebrand Factor A1-glycoprotein Ibalpha-botrocetin complex===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15665869}}
==Disease==
==Disease==
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[[Category: Protein-protein complex]]
[[Category: Protein-protein complex]]
[[Category: Rossmann fold]]
[[Category: Rossmann fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:36:09 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:09:25 2008''

Revision as of 01:09, 29 July 2008

Template:STRUCTURE 1u0n

Contents

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

Template:ABSTRACT PUBMED 15665869

Disease

Known disease associated with this structure: Bernard-Soulier syndrome, type A OMIM:[606672], von Willebrand disease, platelet-type OMIM:[606672], Nonarteritic anterior ischemic optic neuropathy, susceptibility to OMIM:[606672]

About this Structure

1U0N is a Protein complex structure of sequences from Bothrops jararaca and Homo sapiens. 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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