Structural analysis of the transcription environment factors that engage in crosstalk with metabolic pathways

2015 Fiscal Year Final Research Report

• Project Area: Crosstalk of transcriptional control and energy pathways by hub metabolites
• Project/Area Number: 23116007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: Shimizu Toshiyuki 東京大学, 薬学研究科(研究院), 教授 (30273858)
• Co-Investigator(Renkei-kenkyūsha): TOMA Sachiko 東京大学, 大学院薬学系研究科, 助教 (40363535) ; NAKAJIMA Yuka 筑波大学, 生命環境系, 助教 (40399499)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: アルギニンメチル化 / PRMT / 翻訳後修飾 / SAM / X線結晶構造解析

Outline of Final Research Achievements

Arginine methylation is a post-translational modification catalyzed by the protein arginine methyltransferase (PRMT) family. PRMT1, the predominant member, is responsible for most of the arginine methylation in the cell, is ubiquitously expressed. In contrast, much less is known about its closely related family member, PRMT8. PRMT7 has a unique domain structure consisting two tandem core domains.
We determine the structures of PRMT8 and PRMT7. PRMT8 forms novel helical assembly in the crystal. The mutant protein disrupting the helical assembly exhibits a different cellular localization and reduced the methyltransferase activity, suggesting that the higher oligomerization state is necessary for the proper function of PRMT8. The N and C-terminal core domain of PRMT7 formed the hetero core-dimer like structure. SAH was observed only in the N-terminal catalytic domain. The obtained structural feature suggests that C-terminal core domain lacks the function of the methyltransferase activity.

Free Research Field

構造生物学