2009 Fiscal Year Final Research Report
Structural basis for the cleavage of VWF by ADAMTS-13 under shear forces
| Project/Area Number |
20790030
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NISHIDA Noritaka The University of Tokyo, 大学院・薬学系研究科, 助教 (50456183)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 構造生物学 |
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| Research Abstract |
Von Willebrand factor (VWF) mediates platelet adhesion under high shear stress. The activity of VWF is controlled by the ADAMTS13, which cuts the VWF in the force dependent manner. However, the structural basis as to how VWF exposes the cryptic site in the A2 domain for ADAMTS13 is unknown. In this study, I made a recombinant VWF A2 domain, using Pichia Pastorsis. Backbone resonance assignment of A2 domain was established for >80% signals. Based on the chemical shift change induced by low concentration of urea, the a3 and a5 helices and a4less loop, which is proximal to the scissile bond, undergoes a conformational change that would exposes the cleavage site for ADAMTS13.
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[Journal Article] Shimada I "Two-state conformations in the hyarulonan-binding domain regulate CD44 adhesiveness under flow condition"2010
Author(s)
Ogino S, Nishida N, Umemoto R, Suzuki M, Takeda M, Terasawa H, Kitayama J, Matsumoto M, Hayasaka H, Miyasaka M, Shimada I
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Journal Title
Structure 18
Pages: 649-56
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