Structural biology of the mechanism of biomembrane phospholipid biosynthesis by phosphatidylserine decarboxylase

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15734
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Yamagata University
• Principal Investigator: Watanabe Yasunori 山形大学, 理学部, 講師 (30772636)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: X線結晶構造解析 / リン脂質 / PS脱炭酸酵素

Outline of Final Research Achievements

Phosphatidylserine decarboxylase (PSD) is involved in the biosynthesis of phosphatidylethanolamine (PE), one of major phospholipid in biomembrane. However the detailed mechanisms of PE biosynthesis by PSD remain unclear, because the structure of PSD has not been clarified for nearly 50 years since its discovery. In this study, we succeeded for the first time in determining the structures of the apo-form and substrate-bound forms of PSD from Escherichia coli by X-ray crystallography. Mutational analysis based on the determined structures revealed the amino acid residues involved in substrate recognition and the mechanism of membrane binding. These results provide a structural basis for understanding the mechanism of PE biosynthesis by PSDs.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

PEの生合成に関わるPSDは細菌からヒトに至るまで高度に保存されており，リン脂質代謝において重要な役割を果たしている。ヒト由来PSD遺伝子（PISD遺伝子）に変異が導入されることが原因で白内障や骨系統疾患が発症することが報告された。これらは生体膜を構成するリン脂質の代謝の恒常性維持が生命活動に密接に関連していることを示唆している。本研究でのPSDの構造解析研究を通して将来的にはPISD遺伝子の変異によりヒトの疾患が引き起こされる原因の解明につながるであろう。