Elucidation of membrane protein integration mechanism of glycolipid MPIase by using synthetic MPIase library.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K13262
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: Suntory Foundation for Life Sciences
• Principal Investigator: Fujikawa Kohki 公益財団法人サントリー生命科学財団, 生物有機科学研究所・構造生命科学研究部, 研究員 (50755874)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 糖脂質 / 膜タンパク質 / 膜挿入 / シャペロン

Outline of Final Research Achievements

To elucidate the membran protein integration mechanism of glycolipid MPIase, which has the function of inserting membrane proteins of Escherichia coli into membranes, chemical synthesis of various types of analogs, including trisaccharyl pyrophospholipid (mini-MPIase-3), was carried out and it was used for structure-activity relationship studies. As a result, the membrane protein integration mechanism in which the sugar chain of MPIase captures the membrane protein and leads to the inner membrane by suppressing protein aggregation was demonstrated. In addition, the sugar chain of MPIase has chaperone-like activity, GlcNAc 6-OAc group, a carboxy group, and pyrophosphate are essential for the activity, and anchoring MPIase to the membrane contribute increasing the fluidity of the membrane were proved.

Free Research Field

糖鎖合成化学

Academic Significance and Societal Importance of the Research Achievements

これまでに糖脂質が膜タンパク質の膜挿入に関与しているという報告はなく、糖脂質の酵素・シャペロン様の新機能を示すことができた。糖鎖のシャペロン様活性は、タンパク質の凝集抑制(可溶化)剤の開発につながり、タンパク質凝集が引き金になるアルツハイマー病などの疾患の解決にも応用が期待される。また、膜タンパク質を膜挿入する合成分子を初めて創出できた事から、今後、無細胞タンパク質合成系を用いた膜タンパク質の再構成効率を高める分子が多く開発され、再構成の難しい膜タンパク質研究が推進されると期待される。