Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins

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 pathogen manipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to phospha...

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Bibliographic Details
Published in:eLife 2017-04, Vol.6
Main Authors: Yang, Aimin, Pantoom, Supansa, Wu, Yao-Wen
Format: Article
Language:English
Subjects:
Autophagy
Autophagy-Related Protein 8 Family - antagonists & inhibitors
Autophagy-Related Protein 8 Family - chemistry
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Biochemistry
Biophysics and Structural Biology
Biosynthesis
Cell Line
Crystallography, X-Ray
GDI
host-pathogen interaction
Host-Pathogen Interactions
Humans
Legionella
Legionella pneumophila
Legionella pneumophila - physiology
Microtubule-Associated Proteins - antagonists & inhibitors
Microtubule-Associated Proteins - chemistry
Models, Molecular
native chemical ligation
Organelles
Peptides
Phagocytosis
Phosphatidylethanolamine
Phosphatidylethanolamines - metabolism
Phospholipid transfer protein
Protein Conformation
Proteins
Sec14
Statistical analysis
Structure-function relationships
Variance analysis
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Summary: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 pathogen manipulates 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, has evolved a novel mechanism to specifically evade host autophagy.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.23905