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Lift and cut: Anti-host autophagy mechanism of Legionella pneumophila
Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany; Max-Planck-Institute of Molecular Physiology, Dortmund, Germany; Institute of Chemical Biology and Precision Therapy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.ORCID iD: 0000-0002-2573-8736
2017 (English)In: Autophagy, ISSN 1554-8627, E-ISSN 1554-8635, Vol. 13, no 8, p. 1467-1469Article in journal (Refereed) Published
Abstract [en]

RavZ, an effector protein of pathogenic Legionella pneumophila, inhibits host macroautophagy/autophagy by deconjugation of lipidated LC3 proteins from phosphatidylethanolamine (PE) on the autophagosome membrane. The mechanism for how RavZ specifically recognizes and deconjugates the lipidated LC3s is not clear. To understand the structure-function relationship of LC3-deconjugation by RavZ, we prepared semisynthetic LC3 proteins modified with different fragments of PE or 1-hexadecanol (C16). We find that RavZ activity is strictly dependent on the conjugated PE structure and RavZ extracts LC3-PE from the membrane before deconjugation. Structural and biophysical analysis of RavZ-LC3 interactions suggest that RavZ initially recognizes LC3-PE on the membrane via its N-terminal LC3-interacting region (LIR) motif. RavZ specifically targets to autophagosome membranes by interaction with phosphatidylinositol 3-phosphate (PtdIns3P) via its C-terminal domain and association with membranes via the hydrophobic α3 helix. The α3 helix is involved in extraction of the PE moiety and docking of the fatty acid chains into the lipid-binding site of RavZ, which is related in structure to that of the phospholipid transfer protein Sec14. The LIR interaction and lipid binding facilitate subsequent proteolytic cleavage of LC3-PE. The findings reveal a novel mode of host-pathogen interaction.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2017. Vol. 13, no 8, p. 1467-1469
National Category
Biochemistry and Molecular Biology Structural Biology
Identifiers
URN: urn:nbn:se:umu:diva-158840DOI: 10.1080/15548627.2017.1327943ISI: 000409263400015PubMedID: 28598235OAI: oai:DiVA.org:umu-158840DiVA, id: diva2:1314893
Funder
EU, European Research Council, ChemBioAPAvailable from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-13Bibliographically approved

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Wu, Yao-Wen

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