Structural biology of membrane transporters involved in the efflux mechanism of organic molecules

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03640
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Ishitani Ryuichiro 東京大学, 大学院理学系研究科(理学部), 特任教授 (90361568)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Ｘ線結晶構造解析 / 膜タンパク質 / 多剤耐性菌 / 薬物動態

Outline of Final Research Achievements

Living organisms are constantly exposed to toxic organic molecules, and cells have a mechanism to excrete them as a defensive measure. The molecular entity of this efflux mechanism is the membrane protein, the "efflux transporter". In this study, we analyzed the structure of MATE, a multidrug efflux transporter, focusing on the efflux mechanism of organic molecules. For eukaryotic MATE, we determined the structure of the outward opening state of the MATE transporter AtDTX14, from Arabidopsis, and verified the transport mechanism by structure-based mutational analysis. We also analyzed the structure of VcmN, a MATE from a pathogenic bacterium. The results of this structural analysis suggested that VcmN extrudes the substrate by H+-motive force-dependent TM1 bending.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

生体は常に有毒な有機分子にさらされているが、細胞は防御策としてこれらを排出する機構を有している。これらの排出にかかわるMATE輸送体は細胞内外の物質の分布を制御する役割を担うため、その輸送機構を解明することは生命現象を理解するうえで必須であり、さらに医薬への応用などにおいても重要である。