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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2010-3-15
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pubmed:databankReference |
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pubmed:abstractText |
Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 A) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed beta-strand of the C2 domain, Trp(2313)-His(2315). This result indicates that the Trp(2313)-His(2315) segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-10586886,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-10586887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-10800171,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-11418455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-11698391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-11830468,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-15147379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-15184653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-15489168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-16680712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-17583728,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-17646652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-17965321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-18400180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-1846615,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-2110840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-2115693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-3092220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-3128786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-6438526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-6438528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-6782101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-7775440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20089867-9399839
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8824-9
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pubmed:dateRevised |
2011-7-26
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pubmed:meshHeading |
pubmed-meshheading:20089867-Blood Coagulation,
pubmed-meshheading:20089867-Cell Membrane,
pubmed-meshheading:20089867-Crystallography, X-Ray,
pubmed-meshheading:20089867-Factor VIII,
pubmed-meshheading:20089867-Histidine,
pubmed-meshheading:20089867-Humans,
pubmed-meshheading:20089867-Models, Molecular,
pubmed-meshheading:20089867-Phospholipids,
pubmed-meshheading:20089867-Protein Binding,
pubmed-meshheading:20089867-Protein Structure, Tertiary,
pubmed-meshheading:20089867-Risk,
pubmed-meshheading:20089867-Surface Plasmon Resonance,
pubmed-meshheading:20089867-Thromboembolism,
pubmed-meshheading:20089867-Tryptophan,
pubmed-meshheading:20089867-von Willebrand Factor
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pubmed:year |
2010
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pubmed:articleTitle |
Trp2313-His2315 of factor VIII C2 domain is involved in membrane binding: structure of a complex between the C2 domain and an inhibitor of membrane binding.
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pubmed:affiliation |
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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