1sq0: Difference between revisions

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[[Image:1sq0.gif|left|200px]]
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{{STRUCTURE_1sq0|  PDB=1sq0  |  SCENE=  }}  
{{STRUCTURE_1sq0|  PDB=1sq0  |  SCENE=  }}  


'''Crystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution'''
===Crystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution===




==Overview==
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The adhesion of platelets to the subendothelium of blood vessels at sites of vascular injury under high shear conditions is mediated by a direct interaction between the platelet receptor glycoprotein Ibalpha (GpIbalpha) and the A1 domain of the von Willebrand factor (VWF). Here we report the 2.6-A crystal structure of a complex comprised of the extracellular domain of GpIbalpha and the wild-type A1 domain of VWF. A direct comparison of this structure to a GpIbalpha-A1 complex containing "gain-of-function" mutations, A1-R543Q and GpIbalpha-M239V, reveals specific structural differences between these complexes at sites near the two GpIbalpha-A1 binding interfaces. At the smaller interface, differences in interaction show that the alpha1-beta2 loop of A1 serves as a conformational switch, alternating between an open alpha1-beta2 isomer that allows faster dissociation of GpIbalpha-A1, as observed in the wild-type complex, and an extended isomer that favors tight association as seen in the complex containing A1 with a type 2B von Willebrand Disease (VWD) mutation associated with spontaneous binding to GpIbalpha. At the larger interface, differences in interaction associated with the GpIbalpha-M239V platelet-type VWD mutation are minor and localized but feature discrete gamma-turn conformers at the loop end of the beta-hairpin structure. The beta-hairpin, stabilized by a strong classic gamma-turn as seen in the mutant complex, relates to the increased affinity of A1 binding, and the beta-hairpin with a weak inverse gamma-turn observed in the wild-type complex corresponds to the lower affinity state of GpIbalpha. These findings provide important details that add to our understanding of how both type 2B and platelet-type VWD mutations affect GpIbalpha-A1 binding affinity.
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{{ABSTRACT_PUBMED_15039442}}


==Disease==
==Disease==
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[[Category: Stahl, M L.]]
[[Category: Stahl, M L.]]
[[Category: Sullivan, F.]]
[[Category: Sullivan, F.]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 09:00:03 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:34:42 2008''

Revision as of 02:34, 29 July 2008

File:1sq0.png

Template:STRUCTURE 1sq0

Crystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom ResolutionCrystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution

Template:ABSTRACT PUBMED 15039442

DiseaseDisease

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 StructureAbout this Structure

1SQ0 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ibalpha complex reveals conformation differences with a complex bearing von Willebrand disease mutations., Dumas JJ, Kumar R, McDonagh T, Sullivan F, Stahl ML, Somers WS, Mosyak L, J Biol Chem. 2004 May 28;279(22):23327-34. Epub 2004 Mar 23. PMID:15039442

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