1ijk
From Proteopedia
(New page: 200px<br /> <applet load="1ijk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ijk, resolution 2.60Å" /> '''The von Willebrand ...) |
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| - | [[Image:1ijk.gif|left|200px]]<br /> | + | [[Image:1ijk.gif|left|200px]]<br /><applet load="1ijk" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ijk" size=" | + | |
caption="1ijk, resolution 2.60Å" /> | caption="1ijk, resolution 2.60Å" /> | ||
'''The von Willebrand Factor mutant (I546V) A1 domain-botrocetin Complex'''<br /> | '''The von Willebrand Factor mutant (I546V) A1 domain-botrocetin Complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The A1 domain of von Willebrand factor (vWF) mediates platelet adhesion to | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IJK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1IJK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IJK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Bankston, L | + | [[Category: Bankston, L A.]] |
| - | [[Category: Cruz, M | + | [[Category: Cruz, M A.]] |
| - | [[Category: Diacovo, T | + | [[Category: Diacovo, T G.]] |
| - | [[Category: Doggett, T | + | [[Category: Doggett, T A.]] |
[[Category: Fukuda, K.]] | [[Category: Fukuda, K.]] | ||
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
[[Category: c-type lectin fold]] | [[Category: c-type lectin fold]] | ||
[[Category: dinucleotide-binding fold]] | [[Category: dinucleotide-binding fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:12:29 2008'' |
Revision as of 11:12, 21 February 2008
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The von Willebrand Factor mutant (I546V) A1 domain-botrocetin Complex
Contents |
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.
Disease
Known diseases associated with this structure: von Willebrand disease OMIM:[193400]
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
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