1ijk
From Proteopedia
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1auq|1AUQ]], [[1ijb|1IJB]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ijk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ijk OCA], [http://www.ebi.ac.uk/pdbsum/1ijk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ijk RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: von Willebrand disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=193400 193400]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 35: | Line 35: | ||
[[Category: dinucleotide-binding fold]] | [[Category: dinucleotide-binding fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:20:38 2008'' |
Revision as of 18:20, 30 March 2008
| |||||||
| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Related: | 1AUQ, 1IJB
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The von Willebrand Factor mutant (I546V) A1 domain-botrocetin Complex
Overview
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.
About this Structure
1IJK is a Protein complex structure of sequences from Bothrops jararaca and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of von Willebrand factor activation by the snake toxin botrocetin., Fukuda K, Doggett TA, Bankston LA, Cruz MA, Diacovo TG, Liddington RC, Structure. 2002 Jul;10(7):943-50. PMID:12121649
Page seeded by OCA on Sun Mar 30 21:20:38 2008
