1gwb
From Proteopedia
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|PDB= 1gwb |SIZE=350|CAPTION= <scene name='initialview01'>1gwb</scene>, resolution 2.8Å | |PDB= 1gwb |SIZE=350|CAPTION= <scene name='initialview01'>1gwb</scene>, resolution 2.8Å | ||
|SITE= <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+B'>AC2</scene> | |SITE= <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+B'>AC2</scene> | ||
| - | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PT:PLATINUM+(II)+ION'>PT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PT:PLATINUM+(II)+ION'>PT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=STY:TYROSINE-O-SULPHONIC+ACID'>STY</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gwb OCA], [http://www.ebi.ac.uk/pdbsum/1gwb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gwb RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Glycoprotein Ib (GPIb) is a platelet receptor with a critical role in mediating the arrest of platelets at sites of vascular damage. GPIb binds to the A1 domain of von Willebrand factor (vWF-A1) at high blood shear, initiating platelet adhesion and contributing to the formation of a thrombus. To investigate the molecular basis of GPIb regulation and ligand binding, we have determined the structure of the N-terminal domain of the GPIb(alpha) chain (residues 1-279). This structure is the first determined from the cell adhesion/signaling class of leucine-rich repeat (LRR) proteins and reveals the topology of the characteristic disulfide-bonded flanking regions. The fold consists of an N-terminal beta-hairpin, eight leucine-rich repeats, a disulfide-bonded loop, and a C-terminal anionic region. The structure also demonstrates a novel LRR motif in the form of an M-shaped arrangement of three tandem beta-turns. Negatively charged binding surfaces on the LRR concave face and anionic region indicate two-step binding kinetics to vWF-A1, which can be regulated by an unmasking mechanism involving conformational change of a key loop. Using molecular docking of the GPIb and vWF-A1 crystal structures, we were also able to model the GPIb.vWF-A1 complex. | Glycoprotein Ib (GPIb) is a platelet receptor with a critical role in mediating the arrest of platelets at sites of vascular damage. GPIb binds to the A1 domain of von Willebrand factor (vWF-A1) at high blood shear, initiating platelet adhesion and contributing to the formation of a thrombus. To investigate the molecular basis of GPIb regulation and ligand binding, we have determined the structure of the N-terminal domain of the GPIb(alpha) chain (residues 1-279). This structure is the first determined from the cell adhesion/signaling class of leucine-rich repeat (LRR) proteins and reveals the topology of the characteristic disulfide-bonded flanking regions. The fold consists of an N-terminal beta-hairpin, eight leucine-rich repeats, a disulfide-bonded loop, and a C-terminal anionic region. The structure also demonstrates a novel LRR motif in the form of an M-shaped arrangement of three tandem beta-turns. Negatively charged binding surfaces on the LRR concave face and anionic region indicate two-step binding kinetics to vWF-A1, which can be regulated by an unmasking mechanism involving conformational change of a key loop. Using molecular docking of the GPIb and vWF-A1 crystal structures, we were also able to model the GPIb.vWF-A1 complex. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Bernard-Soulier syndrome, type A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]], Nonarteritic anterior ischemic optic neuropathy, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]], von Willebrand disease, platelet-type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Harrison, T.]] | [[Category: Harrison, T.]] | ||
[[Category: Uff, S.]] | [[Category: Uff, S.]] | ||
| - | [[Category: ACY]] | ||
| - | [[Category: NAG]] | ||
| - | [[Category: NDG]] | ||
| - | [[Category: PT]] | ||
| - | [[Category: SO4]] | ||
[[Category: bernard soulier syndrome]] | [[Category: bernard soulier syndrome]] | ||
[[Category: blood coagulation]] | [[Category: blood coagulation]] | ||
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[[Category: von willebrand disease]] | [[Category: von willebrand disease]] | ||
| - | ''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 20:52:39 2008'' |
Revision as of 17:52, 30 March 2008
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| , resolution 2.8Å | |||||||
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| Sites: | |||||||
| Ligands: | , , , , , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF GLYCOPROTEIN 1B
Overview
Glycoprotein Ib (GPIb) is a platelet receptor with a critical role in mediating the arrest of platelets at sites of vascular damage. GPIb binds to the A1 domain of von Willebrand factor (vWF-A1) at high blood shear, initiating platelet adhesion and contributing to the formation of a thrombus. To investigate the molecular basis of GPIb regulation and ligand binding, we have determined the structure of the N-terminal domain of the GPIb(alpha) chain (residues 1-279). This structure is the first determined from the cell adhesion/signaling class of leucine-rich repeat (LRR) proteins and reveals the topology of the characteristic disulfide-bonded flanking regions. The fold consists of an N-terminal beta-hairpin, eight leucine-rich repeats, a disulfide-bonded loop, and a C-terminal anionic region. The structure also demonstrates a novel LRR motif in the form of an M-shaped arrangement of three tandem beta-turns. Negatively charged binding surfaces on the LRR concave face and anionic region indicate two-step binding kinetics to vWF-A1, which can be regulated by an unmasking mechanism involving conformational change of a key loop. Using molecular docking of the GPIb and vWF-A1 crystal structures, we were also able to model the GPIb.vWF-A1 complex.
About this Structure
1GWB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the platelet glycoprotein Ib(alpha) N-terminal domain reveals an unmasking mechanism for receptor activation., Uff S, Clemetson JM, Harrison T, Clemetson KJ, Emsley J, J Biol Chem. 2002 Sep 20;277(38):35657-63. Epub 2002 Jun 26. PMID:12087105
Page seeded by OCA on Sun Mar 30 20:52:39 2008
Categories: Homo sapiens | Single protein | Clemetson, J. | Clemetson, K. | Emsley, J. | Harrison, T. | Uff, S. | Bernard soulier syndrome | Blood coagulation | Cell adhesion | Disease mutation | Glycoprotein | Glycoprotein 1b | Hemostasis | Leucine-rich repeat | Platelet | Polymorphism | Repeat | Signal | Transmembrane | Von willebrand disease
