Structure-function relationships of glycosyltransferases involved in muscular dystrophy disease.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26840029
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: High Energy Accelerator Research Organization
• Principal Investigator: Kuwabara Naoyuki 大学共同利用機関法人高エネルギー加速器研究機構, 物質構造科学研究所, 研究員 (70506253)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 糖転移酵素 / ジストログリカン

Outline of Final Research Achievements

A O-mannose type GalNAc-b1,3-GlcNAc-b1,4-(phosphate-6)-Man (core M3) structure of a-dystroglycan (aDG), a subunit of the complex that is anchored to the cell membrane, directly interacts with laminin. Defects in POMGnT1, a glycosyltransferase that participates in formation of GlcNAc-b1,2-Man glycan, are causally related to muscle-eye-brain disease (MEB), a congenital muscular dystrophy, although the role of POMGnT1 in post-phosphoryl modification of core M3 glycan remains elusive.
we found that the stem domain of POMGnT1 recognizes the b-linked GlcNAc of O-mannose glycan. This recognition may also recruit other enzymes that interact with POMGnT1, which is required for further modification of the core M3 glycan. On the basis of our findings, we propose a mechanism for the deficiency in the post-phosphoryl modification of the glycan observed in POMGnT1 KO mice and MEB patients.

Free Research Field

構造生物科学