Structural basis of the substrate specificity of the alpha-tubulin acetyltransferase

• Project/Area Number: 26440033
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Kyushu University
• Principal Investigator: Yuzawa Satoru 九州大学, 医学研究院, 共同研究員 (40515029)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 翻訳後修飾 / 微小管 / 酵素 / 基質特異性 / X線結晶構造解析 / 分子認識 / 酵素反応 / 蛋白質

Outline of Final Research Achievements

The functions of microtubules are controlled in part by tubulin post-translational modification. αTAT1 is the major α-tubulin acetyltransferase in ciliated organisms and acetylates conserved lysine residue at lysine 40 on α-tubulin proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine. In this study, we determined the crystal structures of αTAT1 bound to its substrate acetyl-CoA or CoA and show the cofactor-mediated stabilization of αTAT1．We also elucidate the recognition of α-tubulin by αTAT1 using wild type and mutant proteins and study on structure of the CoA disulfide bound αTAT1.

Research Products

• [Journal Article] Ric-8A-mediated stabilization of the trimeric G protein subunit Gαi is inhibited by pertussis toxin-catalyzed ADP-ribosylation (2017)
  • Author(s): Kanako Chishiki, Sachiko Kamakura, Junya Hayase, Satoru Yuzawa, Hideki Sumimoto
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 483 Issue: 3 Pages: 941-945
  • DOI: 10.1016/j.bbrc.2017.01.036
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structural basis of cofactor-mediated stabilization and substrate recognition of the α-tubulin acetyltransferase αTAT1 (2015)
  • Author(s): Yuzawa S, Kamakura S, Hayase J, Sumimoto H
  • Journal Title: Biochem J. Volume: 467 Issue: 2 Pages: 103-113
  • DOI: 10.1107/s2053230x14028143
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural basis of cofactor-mediated stabilization and substrate recognition of the α-tubulin acetyltransferase αTAT1 (2015)
  • Author(s): Satoru Yuzawa, Sachiko Kamakura, Junya Hayase and Hideki Sumimoto
  • Journal Title: Biochemical Journal Volume: 467 Issue: 1 Pages: 103-113
  • DOI: 10.1042/bj20141193
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] アダプタータンパク質LGNのTPRドメインによるスキャフォールドタンパク質Frmpd4/Preso1認識の構造基盤 (2015)
  • Author(s): 髙栁宏樹，湯澤聡，住本英樹
  • Organizer: 第38回分子生物学会年会・第88回生化学会大会合同大会BMB2015
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] α-チューブリンアセチル化酵素αTAT1のコファクターによる安定化の構造基盤 (2015)
  • Author(s): 湯澤聡，鎌倉幸子，早瀬純也，住本英樹
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: 徳島市
  • Year and Date: 2015-06-24