Modulation of Membrane Protein Dynamics by Glycan-Galectin Interaction

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19112
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Osaka University
• Principal Investigator: Kabayama Kazuya 大阪大学, 放射線科学基盤機構, 教授 (00399974)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 合成糖鎖 / ガレクチン / ガラクトース / イメージング / galectin-3 / 抗体

Outline of Final Research Achievements

This study aimed to control protein dynamics in living cells through interactions between synthetic glycans and galectins. Internalization control was conducted using not only membrane proteins but also antibodies. Galactose-terminated synthetic glycans were conjugated to an anti-HER2 antibody tagged with a fluorescent probe. When this conjugate was added to HER2-overexpressing cells, internalization was suppressed in the presence of galectin-3, which has a high affinity for galactose, and complement-dependent cytotoxicity was enhanced. Similarly, it was demonstrated through microscopic observation of molecular dynamics that the lateral diffusion of fluorescent labeled membrane proteins modified with galactose-terminated glycans were regulated by galectin-3.

Free Research Field

糖鎖工学

Academic Significance and Societal Importance of the Research Achievements

本研究は合成糖鎖を生細胞上で機能させ、生命現象に関与するタンパク質との相互作用を実証する萌芽的検証実験であり、研究成果を論文として発出できたことは、これまで糖鎖構造の複雑性から詳細な分子構造まで議論できなかった本分野において、学術的に意義深い。また、膜タンパク質の側方拡散制御についても、これまでの遺伝子制御や代謝制御による糖鎖組成変化の複雑さから脱却し、合成糖鎖を用いて明確に糖鎖構造の違いによる相互作用を確認できたことは、当該分野において化学と生物を融合した新たな研究領域の創出に繋がるものと考える。