1auq
From Proteopedia
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|PDB= 1auq |SIZE=350|CAPTION= <scene name='initialview01'>1auq</scene>, resolution 2.3Å | |PDB= 1auq |SIZE=350|CAPTION= <scene name='initialview01'>1auq</scene>, resolution 2.3Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=IUM:URANYL (VI) ION'>IUM</scene> | + | |LIGAND= <scene name='pdbligand=IUM:URANYL+(VI)+ION'>IUM</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1auq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1auq OCA], [http://www.ebi.ac.uk/pdbsum/1auq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1auq RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
von Willebrand Factor (vWF) is a multimeric protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury under conditions of high flow/shear. The A1 domain of vWF (vWF-A1) forms the principal binding site for platelet glycoprotein Ib (GpIb), an interaction that is tightly regulated. We report here the crystal structure of the vWF-A1 domain at 2.3-A resolution. As expected, the overall fold is similar to that of the vWF-A3 and integrin I domains. However, the structure also contains N- and C-terminal arms that wrap across the lower surface of the domain. Unlike the integrin I domains, vWF-A1 does not contain a metal ion-dependent adhesion site motif. Analysis of the available mutagenesis data suggests that the activator botrocetin binds to the right-hand face of the domain containing helices alpha5 and alpha6. Possible binding sites for GpIb are the front and upper surfaces of the domain. Natural mutations that lead to constitutive GpIb binding (von Willebrand type IIb disease) cluster in a different site, at the interface between the lower surface and the terminal arms, suggesting that they disrupt a regulatory region rather than forming part of the primary GpIb binding site. A possible pathway for propagating structural changes from the regulatory region to the ligand-binding surface is discussed. | von Willebrand Factor (vWF) is a multimeric protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury under conditions of high flow/shear. The A1 domain of vWF (vWF-A1) forms the principal binding site for platelet glycoprotein Ib (GpIb), an interaction that is tightly regulated. We report here the crystal structure of the vWF-A1 domain at 2.3-A resolution. As expected, the overall fold is similar to that of the vWF-A3 and integrin I domains. However, the structure also contains N- and C-terminal arms that wrap across the lower surface of the domain. Unlike the integrin I domains, vWF-A1 does not contain a metal ion-dependent adhesion site motif. Analysis of the available mutagenesis data suggests that the activator botrocetin binds to the right-hand face of the domain containing helices alpha5 and alpha6. Possible binding sites for GpIb are the front and upper surfaces of the domain. Natural mutations that lead to constitutive GpIb binding (von Willebrand type IIb disease) cluster in a different site, at the interface between the lower surface and the terminal arms, suggesting that they disrupt a regulatory region rather than forming part of the primary GpIb binding site. A possible pathway for propagating structural changes from the regulatory region to the ligand-binding surface is discussed. | ||
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| - | ==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== | ||
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[[Category: Handin, R.]] | [[Category: Handin, R.]] | ||
[[Category: Liddington, R.]] | [[Category: Liddington, R.]] | ||
| - | [[Category: IUM]] | ||
[[Category: blood coagulation]] | [[Category: blood coagulation]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
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[[Category: willebrand]] | [[Category: willebrand]] | ||
| - | ''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 18:47:52 2008'' |
Revision as of 15:47, 30 March 2008
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| , resolution 2.3Å | |||||||
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
A1 DOMAIN OF VON WILLEBRAND FACTOR
Overview
von Willebrand Factor (vWF) is a multimeric protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury under conditions of high flow/shear. The A1 domain of vWF (vWF-A1) forms the principal binding site for platelet glycoprotein Ib (GpIb), an interaction that is tightly regulated. We report here the crystal structure of the vWF-A1 domain at 2.3-A resolution. As expected, the overall fold is similar to that of the vWF-A3 and integrin I domains. However, the structure also contains N- and C-terminal arms that wrap across the lower surface of the domain. Unlike the integrin I domains, vWF-A1 does not contain a metal ion-dependent adhesion site motif. Analysis of the available mutagenesis data suggests that the activator botrocetin binds to the right-hand face of the domain containing helices alpha5 and alpha6. Possible binding sites for GpIb are the front and upper surfaces of the domain. Natural mutations that lead to constitutive GpIb binding (von Willebrand type IIb disease) cluster in a different site, at the interface between the lower surface and the terminal arms, suggesting that they disrupt a regulatory region rather than forming part of the primary GpIb binding site. A possible pathway for propagating structural changes from the regulatory region to the ligand-binding surface is discussed.
About this Structure
1AUQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib., Emsley J, Cruz M, Handin R, Liddington R, J Biol Chem. 1998 Apr 24;273(17):10396-401. PMID:9553097
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