Elucidation of structural mechanism of substrate selection and secretion signal in T3SS secretion by theoretical and experimental structural biology

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790411
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including Mycology)
• Research Institution: Chiba University
• Principal Investigator: SATO Yoshiharu 千葉大学, 薬学研究科(研究院), 助教 (00554586)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: サルモネラ / III型分泌装置 / エフェクター / 病原因子

Research Abstract

Many bacterial pathogens manipulate cellular functions of host cells by injecting virulence proteins(T3SS effectors) into host cells using T3SS apparatus. Structural modeling analysis and biochemical experiments revealed that substrate selection and the recognition in T3SS secretion are conducted by the similar mechanism as used in the system of AAA+ protease ClpXP-substrate interaction. Based on the findings, structural property analysis was integrated into the effector prediction system, and the prediction accuracy was further improved. Experimental validation for 9 putative Salmonella effectors listed by this program revealed that five novel effectors including STM1239 were confirmed to secrete into supernatant of culture media.

Research Products

• [Journal Article] Methylation of 23S rRNA nucleotide G748 by RlmAII methyltransferase renders Streptococcus pneumoniae telithromycin susceptible (2013)
  • Author(s): Takaya, A., Sato, Y., Shoji, T., Yamamoto, T
  • Journal Title: Antimicrob Agents Chemother Volume: 57(8) Pages: 3789-3796
  • Peer Reviewed
• [Journal Article] PCDq : human protein complex database with quality index which summarizes different levels of evidences of protein complexes predicted from H-Invitational protein-protein interactions integrative dataset (2012)
  • Author(s): Kikugawa, S., Nishikata, K., Murakami, K., Sato, Y., Suzuki, M., Altaf-Ul-Amin, Md., Kanaya, S., Imanishi, T
  • Journal Title: BMC systems biology Volume: 6(Suppl 2) Pages: S7
  • Peer Reviewed
• [Journal Article] Prediction of protein-destabilizing polymorphisms by manual curation with protein structure (2012)
  • Author(s): Gough, CA., Homma, K., Yamaguchi-Kabata, Y., Shimada, MK., Chakraborty, R., Fujii, Y., Iwama, H., Minoshima, S., Sakamoto, S., Sato, Y. et al
  • Journal Title: PLoS One Volume: 7(11) Pages: e50445
  • Peer Reviewed
• [Journal Article] Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of Theileria-induced leukocyte transformation (2012)
  • Author(s): Hayashida, K., Hara, Y., Abe, T., Yamasaki, C., Toyoda, A., Kosuge, T., Suzuki, Y., Sato, Y. et al
  • Journal Title: MBio Volume: 3(5) Pages: e00204-e002012
  • Peer Reviewed
• [Presentation] FliT enhances the ClpXP-catalyzed degradation of master regulator FlhD_4C_2 in Salmonella (2014)
  • Author(s): 佐藤慶治,高屋明子,山本友子
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京タワーホール船堀
  • Year and Date: 2014-03-28
• [Presentation] FliT fine-tunes the flagellar biogenesis by enhancing the ClpXP-catalyzed degradation of master regulator FlhD_4C_2. EMBO workshop on AAA+ proteins (2013)
  • Author(s): Akiko Takaya, Yoshiharu Sato, Tomoko Yamamoto
  • Organizer: from mechanism and disease to targets
  • Place of Presentation: Commundo Hotel Neuss, Germany
  • Year and Date: 20130915-19
• [Presentation] 協調的認識により調節されるAAA+プロテアーゼClpXPの基質特異性 (2013)
  • Author(s): 佐藤慶治、唐田清信、高屋明子、山本友子
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉幕張メッセ
  • Year and Date: 20130318-20
• [Presentation] Substrate specificity of AAA+ protease ClpXP determined by bipertite recognition (2012)
  • Author(s): Yoshiharu Sato, Akiko Takaya, Tomoko Yamamoto
  • Organizer: 第35回日本分子生物学会年会口頭発表
  • Place of Presentation: 福岡福岡国際会議場・マリンメッセ福岡
  • Year and Date: 20121211-12
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/bisei/
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/bisei/software/