Development of a sugar tyoe discrimination in protein glycosylation based on protein subcellular localization

• Project/Area Number: 19K20410
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: Aoyama Gakuin University
• Principal Investigator: Etchuya Kenji 青山学院大学, 理工学部, 助教 (90806499)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 糖鎖修飾 / バイオインフォマティクス / 細胞内局在 / タンパク質 / 糖鎖 / タンパク質翻訳後修飾 / glycosylation / prediction method / bioinformatics / 糖種判別法 / Glycosylation / Bioinformatics / Prediction method / Subcellular localization / Sugar chain

Outline of Research at the Start

タンパク質の糖鎖修飾は代表的な翻訳後修飾のひとつであり、糖鎖はタンパク質の機能を制御する重要な分子である。しかしながら、既存の研究では糖鎖修飾がタンパク質の細胞内局在の過程で起こるという一面は考慮されておらず、タンパク質の細胞内での動きに着目した糖種解析が必要不可欠である。
本研究ではまず、バイオインフォマティクス技術を用いて、タンパク質細胞内局在経路と糖種との相関を明らかにし、既存の糖鎖修飾情報に加え局在情報を包括した知識ベースの開発を行う。次に、糖種分布を学習データとして、糖鎖修飾糖種判別法を開発し、細胞内の糖タンパク質の局在化経路と糖鎖修飾を可視化するWebツールの開発を目指す。

Outline of Final Research Achievements

Glycoproteins with O-glycosylation from Uniprot KB/Swiss-Prot were classified according to signal sequences and O-glycosylations. Datasets were classified into four groups including intracellular, secretory, signal-anchor, and transmembrane proteins based on the signal peptides and transmembrane domains. The distribution of sugar chains differed depending on the intracellular localization, and specific sugar chain modifications were observed in the nucleus, cytoplasm, and mitochondria. This results shown that the O-glycosylation of sugar chains discrimination methods could be applied to developing a highly accurate sugar species discrimination method.

Academic Significance and Societal Importance of the Research Achievements

細胞内の糖鎖修飾システムを考える上で、タンパク質が翻訳後に修飾を受けることに焦点を合わせたタンパク質の細胞内局在性に寄与する分類と糖種との相関をもとに、タンパク質の細胞内局在に応じた糖鎖修飾分布を明らかにすることは重要である。タンパク質の糖鎖修飾を高精度で判別できる手法の開発により、当該タンパク質がどの糖種を修飾されるのか、高精度で予測できることにより、近年のIT分野の著しい発展から地図アプリにより渋滞が回避できるように、糖種分布マップに沿って細胞内局在シグナルをタンパク質に導入することで、目的の糖種のみを回避するようなタンパク質デザインが可能となる。

Research Products

• [Journal Article] Sugar Type Discrimination methods of Protein Sugar Modifications based on Subcellular Localization (2022)
  • Author(s): Kenji Etchuya, Makoto Ohta, Yuri Mukai
  • Journal Title: Proceedings of the 22th International Symposium on Advanced Fluid Information Volume: - Pages: 89-90
  • Peer Reviewed
• [Journal Article] Sugar Type Discrimination of Protein Sugar Modification based on Subcellular Localization (2021)
  • Author(s): K. Etchuya, M. Doi, Y. Mukai
  • Journal Title: Proceedings of the Eighteenth International Conference on Flow Dynamics Volume: 1 Pages: 442-443
  • Peer Reviewed / Open Access
• [Journal Article] Development of Sugar Type Distribution by Glycosylation Based on Protein Subcellular Localization (2019)
  • Author(s): Kenji Etchuya, Makoto Ohta, Yuri Mukai
  • Journal Title: Proceedings of the 19th International Conference on Flow Dynamics Volume: - Pages: 170-171
  • Peer Reviewed / Open Access
• [Presentation] Sugar Type Discrimination methods of Protein Sugar Modifications based on Subcellular Localization (2022)
  • Author(s): Kenji Etchuya, Makoto Ohta, Yuri Mukai
  • Organizer: The 19th International Conference on Flow Dynamics (ICFD2022)
  • Int'l Joint Research
• [Presentation] Sugar Type Discrimination of Protein Sugar Modification based on Subcellular Localization (2021)
  • Author(s): K. Etchuya, M. Doi, Y. Mukai
  • Organizer: Eighteenth International Conference on Flow Dynamics, Sendai
  • Int'l Joint Research / Invited
• [Presentation] evelopment of sugar type distribution by glycosylation based on protein subcellular localization (2020)
  • Author(s): K. ETCHUYA, M. Ohta, Y. MUKAI
  • Organizer: Proceedings of the Twentieth International Symposium on Advanced Fluid Information
  • Int'l Joint Research
• [Presentation] he Role of Signal-anchor Region of Type II Transmembrane Protein in Subcellular Localization (2020)
  • Author(s): Y. Mukai, T. Kikegawa, M. Ohta and K. Etchuya
  • Organizer: Proceedings of the Twentieth International Symposium on Advanced Fluid Information
  • Int'l Joint Research
• [Presentation] Development of Sugar Type Distribution by Glycosylation Based on Protein Subcellular Localization (2019)
  • Author(s): Kenji Etchuya, Makoto Ohta, Yuri Mukai
  • Organizer: International Conference on Flow Dynamics 2019
  • Int'l Joint Research
• [Book] 『膜タンパク質工学ハンドブック (第2編5節 膜タンパク質を対象としたアミノ酸配列解析とその応用)』 (2020)
  • Author(s): 分担執筆: 越中谷 賢治, 向井 有理, 園山正史
  • Total Pages: 624
  • Publisher: (株)エヌ・ティー・エス
  • ISBN: 9784860435370
• [Book] 膜タンパク質ハンドブック (2020)
  • Author(s): 分担執筆 越中谷賢治 他
  • Total Pages: 535
  • Publisher: 株式会社エヌ・ティー・エス
  • ISBN: 9784860435370