How does an intracellular glutamine sensor achieve "specific and weak binding to glutamine?"

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Tanigawa Mirai 浜松医科大学, 医学部, 特任助教 (50553658)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: TORC1 / アミノ酸 / センサー / 代謝制御 / ラパマイシン

Outline of Final Research Achievements

This study provides molecular mechanis of how Pib2 senses intracellular glutamine levels and controls the activity of TORC1, a master regulator of metabolic control.
We elucidated the regions of Pib2 responsible for glutamine sensing, TORC1 binding, and TORC1 activation, respectively. Furthermore, we found that Pib2 does not undergo major conformational changes in the presence of high concentrations of glutamine, although, folding state of Pib2 changes slightly in a glutamine-specific manner. These results suggest a model in which Pib2-TORC1 binding is induced by a slight change in the folding state of Pib2 induced by glutamine binding.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により「天然変性タンパク質が高濃度の細胞内メタボライトを特異的に検知し、代謝制御のハブとなる因子を直接に制御する」という新たな代謝制御機構のモデルを提示することができた。Pib2がTORC1 を活性化するメカニズムを利用して、人為的にTORC1 活性を制御し、代謝をコントロールする方法開発の新たな基盤を提供することができた。