title: Elucidation of the anti-autophagy mechanism of theLegionellaeffector RavZ using semisynthetic LC3 proteins.
abstract: Autophagy is a conserved cellular process involved in the elimination of proteins and organelles. It is also used to combat infection with pathogenic microbes. The intracellular pathogenLegionella pneumophilamanipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to phosphatidylethanolamine (PE) on autophagosomal membranes. To understand how RavZ recognizes and deconjugates LC3-PE, we prepared semisynthetic LC3 proteins and elucidated the structures of the RavZ:LC3 interaction. Semisynthetic LC3 proteins allowed the analysis of structure-function relationships. RavZ extracts LC3-PE from the membrane before deconjugation. RavZ initially recognizes the LC3 molecule on membranes via its N-terminal LC3-interacting region (LIR) motif. The RavZ α3 helix is involved in extraction of the PE moiety and docking of the acyl chains into the lipid-binding site of RavZ that is related in structure to that of the phospholipid transfer protein Sec14. Thus,Legionellahas evolved a novel mechanism to specifically evade host autophagy.
authors.affiliation: Institute of Chemical Biology and Precision Therapy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.|Max-Planck-Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Aimin
authors.identifier: 0000-0002-2240-5549
authors.initials: A
authors.lastname: Yang
authors.affiliation: Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.|Max-Planck-Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Supansa
authors.identifier: 0000-0001-9630-1999
authors.initials: S
authors.lastname: Pantoom
authors.affiliation: Institute of Chemical Biology and Precision Therapy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.|Max-Planck-Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Yao-Wen
authors.identifier: 0000-0002-2573-8736
authors.initials: YW
authors.lastname: Wu
mesh_terms: D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D018360:Crystallography, X-Ray; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D000071190:Autophagy-Related Protein 8 Family; D001426:Bacterial Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine
keywords: GDI; Legionella pneumophila; Sec14; autophagy; biochemistry; biophysics; host-pathogen interaction; native chemical ligation; none; structural biology