Structural biology of Shigella effectors to elucidate the molecular mechanisms of substrate recognition and infection

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04341
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: University of Hyogo
• Principal Investigator: MIZUSHIMA TSUNEHIRO 兵庫県立大学, 生命理学研究科, 教授 (90362269)
• Co-Investigator(Renkei-kenkyūsha): KIM Minsoo 京都大学, 白眉センター, 特定准教授 (50466835)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: エフェクター / X線結晶構造解析 / ユビキチン修飾経路 / 赤痢菌 / ユビキチンリガーゼ

Outline of Final Research Achievements

Pathogenic bacteria such as Shigella, deliver a variety of virulence factors, called effectors, into host cells via the type III secretion system. These effectors mimic or hijack host proteins and modulate host signaling pathways to promote bacterial infection. To elucidate the molecular mechanisms of Shigella flexneri effectors such as OspI and IpaH9.8, we performed the structural and functional analyses of them. OspI deamidates of Ubc13, thereby disrupting TRAF6 activation and dampening host inflammatory responses. IpaH9.8 and IpaH1.4 possessing E3 ligase activity, dampen the NF-kappaB-mediated inflammatory response. We determined the crystal structures of deamidated Ubc13 and substrate recognition domain of IpaH9.8. These structures provide the substrate recognition and inhibition mechanisms of immune response.

Free Research Field

構造生物学