Structure-affinity relationship between the N-glycan of pancreatic glycoprotein GP2 and bacterial lectin FimH

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20563
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0601:Agricultural chemistry and related fields
• Research Institution: Fukushima University
• Principal Investigator: NISHIO Shunsuke 福島大学, 食農学類附属発酵醸造研究所, 特任講師 (20825880)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: GP2 / FimH / 腸内細菌 / レクチン / バイオレイヤー干渉法 / ハイマンノース型糖鎖

Outline of Final Research Achievements

Glycoprotein 2 (GP2) is a secreted protein in response to intestinal inflammation and prevents bacterial colonization of intestinal epithelial cells. GP2 binds to the bacterial fimbria protein FimH. FimH-GP2 interaction is presumed to be mediated by the high mannose N-glycans of GP2, although the actual binding mode is unknown. Human and mouse GP2 were expressed and purified using mammalian cells, and their binding to FimH was measured by biolayer interferometry. Human GP2 contains a novel glycan-attached site where FimH binds in addition to a known high mannose N-glycan binding domain. In contrast, the mouse GP2 expressed in mammalian cells did not have high mannose N-glycans, and there was no binding to FimH.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

FimHと特異的に結合する糖は感染防御に対する治療法の一つとなりうる。本研究によって確立されたGP2とFimHとの定量的な結合解析は、FimHと糖鎖の結合のみに焦点を当てたこれまでの糖の探索方法に比べ、より生体での反応を模倣した、高機能な糖および糖含有食品を見出すことが可能となる。これは、農学から医学にわたる広範な分野への波及効果が期待できる。