Mechanism of lifespan determination of glycoproteins by N-glycans

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Uemura Satoshi 東北医科薬科大学, 医学部, 講師 (10399975)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アスパラギン結合型糖鎖 / 糖転移酵素 / マンナン修飾 / 出芽酵母

Outline of Final Research Achievements

In this study, we investigated whether the glycans attached to asparagine residues of proteins are involved in determining the lifespan. The target proteins were two yeast glycosyltransferases, Sur1 and Csh1, which synthesize glycosphingolipids in the Golgi apparatus. Although the amino acid sequences of these enzymes are very similar, the intracellular stability of Sur1 was significantly higher than that of Csh1. This difference in stability was not caused by the N-glycan of mannan-type, which has a unique structure, attached to only Csh1. However, the stability of the Sur1 mutant, in which the N-glycan of mannan-type was artificially introduced into Sur1, was markedly reduced. Therefore, these results suggest that the N-glycan of mannan-type affected the enzyme stability via the conformational changes.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、出芽酵母において、細胞外に分泌されるタンパク質に結合するマンナン型糖鎖が、なぜ細胞内に留まる糖転移酵素Csh1に結合しているのか、という長年の疑問に対する答えが出せたことは学術的に意義がある。このマンナン型糖鎖が作られるかどうかは、その糖鎖結合位置だけで決まるという事実は、細胞内に留まるタンパク質の中にマンナン型糖鎖を持つものがまだ眠っている可能性を期待させるものである。また、細胞内タンパク質に結合するマンナン型糖鎖がタンパク質の安定性に影響を与えることを明らかにできたことも重要な一歩である。