Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor.

• Project/Area Number: 20570120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: AKIYAMA Masashi National Cardiovascular Center Research Institute, 分子病態部, 室長 (30298179)
• Co-Investigator(Kenkyū-buntansha): KOKAME Koichi 独立行政法人国立循環器病研究センター, 分子病態部, 室長 (40270730) ; TAKEDA Soichi 独立行政法人国立循環器病研究センター, 分子病態部, 室長 (80332279)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 分子認識及び相互作用 / ADAMTS13 / VWF / 結晶構造 / P475S遺伝子多型 / エクソサイト

Research Abstract

We determined crystal structures of an exosite-containing human ADAMTS13 fragment (residues 287-685) required for the cleavage of von Willebrand factor (VWF). We identified 3 VWF-binding exosites on the linearly aligned discontinuous surfaces of the multiple domains traversing the W-shaped molecule. This arrangement suggests that these exosites bind collaboratively to multiple discontinuous regions of VWF.

Research Products

• [Journal Article] VWF切断酵素ADAMTS13のエキソサイト認識機構 (2010)
  • Author(s): 秋山正志、武田壮一、小亀浩市、高木淳一、宮田敏行
  • Journal Title: 生化学 第82巻、第10号 Pages: 950-956
  • NAID: 10027502769
• [Journal Article] ADAMTS13のフォンビルブランド因子認識機構の構造学的基盤 (2010)
  • Author(s): 秋山正志
  • Journal Title: 日本血栓止血学会誌 第21巻、第3号 Pages: 319-326
  • NAID: 10026400518
• [Journal Article] VWF切断酵素ADAMTS13のエキソサイト認識機構 (2010)
  • Author(s): 秋山正志
  • Journal Title: 生化学 Volume: 82 Pages: 950-956
  • NAID: 10027502769
• [Journal Article] ADAMTS13のフォンビルブランド因子認識機構の構造学的基盤 (2010)
  • Author(s): 秋山正志
  • Journal Title: 日本血栓止血学会誌 Volume: 21 Pages: 319-326
  • NAID: 10026400518
• [Journal Article] Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor. (2009)
  • Author(s): Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T.
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 19274-19279
  • NAID: 10026400518
• [Journal Article] Production, crystallization and preliminary crystallographic analysis of an exosite-containing fragment of human von Willebrand factor-cleaving proteinase ADAMTS13. (2009)
  • Author(s): Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T.
  • Journal Title: Acta crystallogr Sect F 65 Pages: 739-742
• [Journal Article] Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor. (2009)
  • Author(s): Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T
  • Journal Title: Proc Natl Acad Sci USA 106(46): Pages: 19274-19279
  • NAID: 10026400518
  • Peer Reviewed
• [Journal Article] Production, crystallization and preliminary crystallographic analysis of an exosite-containing fragment of human von Willebrand factor-cleaving proteinase ADAMTS13. (2009)
  • Author(s): Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun 65(Pt7) Pages: 739-742
  • Peer Reviewed
• [Journal Article] The dorsomedial hypothalamic nucleus is not necessary for food-anticip atory circadian rhythms of behavior, temperature or clock gene expression in mice. (2009)
  • Author(s): Moriya T, Aida R, Kudo T, Akiyama M, Doi M, Hayasaka N, Nakahata N, Mistlberger R, Okamura H, Shibata S
  • Journal Title: Eur J Neurosci 29(7) Pages: 1447-1460
  • Peer Reviewed
• [Journal Article] Macrophage inhibitory cytokine MIC-1 is upregulated by short-wavelength light in cultured normal human dermal fibroblasts. (2009)
  • Author(s): Akiyama M, Okano K, Fukada Y, Okano T.
  • Journal Title: FEBS Lett. 583 Pages: 933-937
  • Peer Reviewed
• [Journal Article] ADAMTS13 P475S polymorphism causes a lowered enzymatic activity and urea lability in vitro. (2008)
  • Author(s): Akiyama M, Kokame K, Miyata T.
  • Journal Title: J. Thromb. Haemost. 144 Pages: 742-754
  • Peer Reviewed
• [Presentation] Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor. (2010)
  • Author(s): 秋山正志
  • Organizer: 第33回日本血栓止血学会学術集会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2010-04-22
• [Presentation] Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor.(受賞講演) (2010)
  • Author(s): 秋山正志、武田壮一、小亀浩市、高木淳一、宮田敏行
  • Organizer: 第33回日本血栓止血学会学術集会
  • Place of Presentation: 鹿児島市
• [Presentation] ADAMTS13非触媒ドメインの結晶構造解析とvon Willebrand因子に対する複数の非連続エキソサイトの同定 (2009)
  • Author(s): 秋山正志、武田壮一、小亀浩市、高木淳一、宮田敏行
  • Organizer: 第82回 日本生化学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-10-23
• [Presentation] Crystal structre of the exosite-containing fragment of ADAMTS13. (2009)
  • Author(s): Akiyama M, Takeda S, Kokame K, Takagi T, Miyata T
  • Organizer: XXII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: アメリカ・ボストン
  • Year and Date: 2009-07-13
• [Presentation] X線解析によるADAMTS13の部分立体構造の決定とエキソサイトの同定 (2009)
  • Author(s): 秋山正志、武田壮一、小亀浩市、高木淳一、宮田敏行
  • Organizer: 第32回 日本血栓止血学会学術総会
  • Place of Presentation: 北九州市
  • Year and Date: 2009-06-04
• [Presentation] ADAMTS13非触媒ドメインの結晶構造解析とvon Willebrand因子に対する複数の非連続エキソサイトの同定(ポスター) (2009)
  • Author(s): 秋山正志、武田壮一、小亀浩市、高木淳一、宮田敏行
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸市
• [Presentation] Identification of multiple discontinuous exosites of ADAMTS13.(ポスター) (2009)
  • Author(s): Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T
  • Organizer: The MMP Gordon Research Conference 2009
  • Place of Presentation: スイス・Les Diableret市
• [Presentation] X線解析によるADAMTS13の非触媒ドメインの構造決定とエキソサイトの同定(口演) (2009)
  • Author(s): 秋山正志.
  • Organizer: 第7回血液・血管オルビス
  • Place of Presentation: 東京都
• [Presentation] Crystal structure of the exosites-containing fragment of ADAMTS13.(口演、Abstract Symposia) (2009)
  • Author(s): Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T
  • Organizer: XXII Congress of the International Society on Thrombosis and Haemositasis
  • Place of Presentation: アメリカ・ボストン市
• [Presentation] X線解析によるADAMTS13の部分立体構造の決定とエキソサイトの同定(口演) (2009)
  • Author(s): 秋山正志、武田壮一、小亀浩市、高木淳一、宮田敏行
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州市
• [Remarks] ホームページ等
  • URL: http://www.ncvc.go.jp/res/divisions/etiology/index.html
• [Remarks]
  • URL: http://www.ncvc.go.jp/res/divisions/etiology/index.html