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-Structure paper
タイトル | Dimeric Organization of Blood Coagulation Factor VIII bound to Lipid Nanotubes. |
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ジャーナル・号・ページ | Sci Rep, Vol. 5, Page 11212, Year 2015 |
掲載日 | 2015年6月17日 |
著者 | Daniela Dalm / Jesus G Galaz-Montoya / Jaimy L Miller / Kirill Grushin / Alex Villalobos / Alexey Y Koyfman / Michael F Schmid / Svetla Stoilova-McPhie / |
PubMed 要旨 | Membrane-bound Factor VIII (FVIII) has a critical function in blood coagulation as the pro-cofactor to the serine-protease Factor IXa (FIXa) in the FVIIIa-FIXa complex assembled on the activated ...Membrane-bound Factor VIII (FVIII) has a critical function in blood coagulation as the pro-cofactor to the serine-protease Factor IXa (FIXa) in the FVIIIa-FIXa complex assembled on the activated platelet membrane. Defects or deficiency of FVIII cause Hemophilia A, a mild to severe bleeding disorder. Despite existing crystal structures for FVIII, its membrane-bound organization has not been resolved. Here we present the dimeric FVIII membrane-bound structure when bound to lipid nanotubes, as determined by cryo-electron microscopy. By combining the structural information obtained from helical reconstruction and single particle subtomogram averaging at intermediate resolution (15-20 Å), we show unambiguously that FVIII forms dimers on lipid nanotubes. We also demonstrate that the organization of the FVIII membrane-bound domains is consistently different from the crystal structure in solution. The presented results are a critical step towards understanding the mechanism of the FVIIIa-FIXa complex assembly on the activated platelet surface in the propagation phase of blood coagulation. |
リンク | Sci Rep / PubMed:26082135 / PubMed Central |
手法 | EM (サブトモグラム平均) / EM (らせん対称) |
解像度 | 15.5 - 21.0 Å |
構造データ | EMDB-3026: EMDB-3027: |
由来 |
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