Molecular mechanisms underlying the sorting of bacterial lipoproteins.

• Project/Area Number: 22380049
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied microbiology
• Research Institution: Morioka College
• Principal Investigator: TOKUDA Hajime 盛岡大学, 栄養学部, 教授 (40125943)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2013: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: Lolシステム / リポ蛋白質 / 膜局在化 / ペリプラズム / 分子シャペロン / 細胞表層構造 / ABCトランスポーター / 阻害剤 / エンベロープストレス / Lo1システム / 膜局在 / 光化学架橋

Outline of Final Research Achievements

The Lol system catalyzing the sorting of lipoproteins from the inner to outer membranes was studied and the following five major findings were obtained. (1) LolC and LolD are functionally different to each other although their structures are similar. (2) Detailed molecular events involving lipoproteins, LolCDE, LolA, and LolB were revealed. (3) Defective lipoprotein sorting induces the Rcs stress response system. (4) The site of LolB required for membrane targeting was identified. (5) Chemicals, which inhibit the function of LolC and LolE, were found.

Research Products

• [Journal Article] Small molecule inhibitors of Gram-negative lipoprotein trafficking discovered by phenotypic screening. (2015)
  • Author(s): McLeod, S. M., Fleming, P. R., MacCormack, K., McLaughlin, R. E., Whiteaker, J. D., Narita, S., Mori, M., Tokuda, H., and Miller, A. A.
  • Journal Title: J. Bacteriol. Volume: 197 Issue: 6 Pages: 1075-1082
  • DOI: 10.1128/jb.02352-14
  • Peer Reviewed
• [Journal Article] Brown, D. G., and McLeod, S. M. Novel antibacterial targets and compounds revealed by a high throughput cell wall reporter assay. (2015)
  • Author(s): Nayar, A. S., Dougherty, T. J., Ferguson, K. E., Granger, B. A., McWilliams, L., Stacey, C., Leach, L. J., Narita, S., Tokuda, H., Miller, A. A.
  • Journal Title: J. Bacteriol. Volume: 197
  • Peer Reviewed
• [Journal Article] Roles of the protruding loop of factor B essential for the localization of lipoproteins (LolB) in the anchoring of bacterial triacylated proteins to the outer membrane. (2014)
  • Author(s): Hayashi, Y., Tsurumizu, R., Tsukahara, J., Takeda, K., Narita, S., Mori, M., Miki, K., and Tokuda, H.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 15 Pages: 10530-10539
  • DOI: 10.1074/jbc.m113.539270
  • Peer Reviewed
• [Journal Article] Functional differentiation of structurally similar membrane subunits of the ABC transporter LolCDE complex. (2013)
  • Author(s): Mizutani, M., Mukaiyama, K., Xiao, J., Mori, M., Satou, R., Narita, S., Okuda, S., and Tokuda, H.
  • Journal Title: FEBS Lett. Volume: 587 Issue: 1 Pages: 23-29
  • DOI: 10.1016/j.febslet.2012.11.009
  • Peer Reviewed
• [Journal Article] Glycolipozyme MPIase is essential for topology inversion of SecG during preprotein translocation (2012)
  • Author(s): Moser, M., Nagamori, S., Huber, M., Tokuda, H., Nishiyama, K.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: (in press) Issue: 24 Pages: 9734-9739
  • DOI: 10.1073/pnas.1303160110
  • Peer Reviewed
• [Journal Article] Defective lipoprotein sorting induces lolA expression through the Rcs stress response phosphorelay system. (2012)
  • Author(s): Tao, K., Narita, S., and Tokuda, H.
  • Journal Title: J. Bacteriol. Volume: (in press) Issue: 14 Pages: 3643-3650
  • DOI: 10.1128/jb.00553-12
  • Peer Reviewed
• [Journal Article] MPIase is a glycolipozyme essential for membrane protein integration (2012)
  • Author(s): Nishiyama, K., Maeda,M., Yanagisawa,K., Nagase, R., Komura, H., Iwashita, T., Yamagaki, T., Kusumoto, S., Tokuda, H., Shimamoto, K.
  • Journal Title: Nat. Commun Volume: 3 Issue: 1 Pages: 1-10
  • DOI: 10.1038/ncomms2267
  • NAID: 120007179832
  • Peer Reviewed
• [Journal Article] Multiple SecA molecules drive protein translocation across a single translocon with SecG inversion (2012)
  • Author(s): Morita, K., Tokuda, H. and Nishiyama, K.
  • Journal Title: J. Biol. Chem Volume: 287巻 Issue: 1 Pages: 455-464
  • DOI: 10.1074/jbc.m111.301754
  • Peer Reviewed
• [Journal Article] Lipoprotein Sorting in Bacteria (2011)
  • Author(s): Okuda, S., Tokuda, H.
  • Journal Title: Annu.Rev.Microbiol. Volume: 65 Pages: 239-259
  • Peer Reviewed
• [Journal Article] Overexpression of LolCDE allows deletion of the Escherichia coli gene encoding apolipoprotein N-acyltransferase (2011)
  • Author(s): Narita, S., Tokuda, H.
  • Journal Title: J.Bacteriol. Volume: 193 Pages: 4832-4840
  • Peer Reviewed
• [Journal Article] Biogenesis and membrane targeting of lipoproteins (2010)
  • Author(s): Narita, S., Tokuda, H.
  • Journal Title: Escherichia coli and Salmonella ; cellular and molecular biology Volume: Chapter4.3.7(online journal)
  • Peer Reviewed
• [Journal Article] Novel mutations of the LolCDE complex causing outer membrane localization of lipoproteins despite their inner membrane retention signals (2010)
  • Author(s): Sakamoto, C, Satou, R., Tokuda, H., Narita, S.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 401 Pages: 586-591
  • Peer Reviewed
• [Journal Article] A periplasmic LolA derivative with a lethal disulfide bond activates the Cpx stress response system (2010)
  • Author(s): Tao, K., Watanabe, S., Narita, S., Tokuda, H.
  • Journal Title: J.Bacteriol. Volume: 192 Pages: 5657-5662
  • Peer Reviewed
• [Presentation] 生育条件の変化に応答したLpp-ペプチドグリカントランスペプチダーゼ遺伝子の発現調節 (2012)
  • Author(s): 青木将、福本玲、徳田元、松山伸一
  • Organizer: 日本農芸化学会
  • Place of Presentation: 京都女子大学
  • Year and Date: 2012-03-24
• [Presentation] 多彩な機能を有するリポ蛋白質の膜局在化を触媒するLol経路
  • Author(s): 徳田 元
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東北大学
  • Invited
• [Presentation] 大腸菌外膜リポ蛋白質輸送不全によるRcsリン酸リレー系に依存したlolA転写活性化の機構
  • Author(s): 垰 和之、徳田 元
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東北大学
• [Book] Bacterial Membranes: Structural and Molecular Biology (2014)
  • Author(s): Tokuda, H., Sander, P., Lee, B. L., Okuda, S., Grau, T., Tschumi, A., Brülle, J. K., Kurokawa, K., and Nakayama, H.
  • Total Pages: 500
  • Publisher: Caiser Academic Press
• [Book] Bacterial Lipoproteins ; Biogenesis, Trafficking and Function (2012)
  • Author(s): Tokuda, H., 他8名
  • Publisher: Horizon Scientific Press(in press)
• [Book] Methods in Molecular Biology ; Protein Secretion (2010)
  • Author(s): Narita, S., Tokuda, H.
  • Publisher: Sorting of bacterial lipoproteins to the outer membrane by the Lol system
• [Remarks] 栄養科学部栄養科学科徳田研究室
  • URL: http://www.morioka-u.ac.jp/UV_ns/tokuda_lab/study.html
• [Remarks] 徳田研究室ホームページ
  • URL: http://www.morioka-u.ac.jp/UV_ns/tokuda_lab/
• [Remarks]
  • URL: http://www.morioka-u.ac.jp/UV_ns/tokuda_lab/
• [Remarks]
  • URL: http://www.morioka-u.ac.jp/UV_ns/tokuda_lab/