The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs
| Autor: | Vladimir Shteyn, Craig R. Roy, Thomas J. Melia, Racquel Kim Sherwood, Karlina J. Kauffman, Karin M. Reinisch, Florian A. Horenkamp, Lara J. Kohler, Kathryn P. Krueger |
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| Rok vydání: | 2015 |
| Předmět: |
Autophagosome
ATG8 Legionella Plasma protein binding Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Phosphatidylinositol Phosphates Phagosomes Autophagy Animals Protein Interaction Domains and Motifs Molecular Biology 030304 developmental biology 0303 health sciences Effector 030302 biochemistry & molecular biology Membrane Proteins Intracellular Membranes Cell Biology Membrane transport Cell biology Transport protein Protein Transport Membrane protein Microtubule-Associated Proteins Protein Binding Developmental Biology |
| Zdroj: | Developmental Cell. 34:569-576 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2015.08.010 |
| Popis: | SummaryAutophagy is a conserved membrane transport pathway used to destroy pathogenic microbes that access the cytosol of cells. The intracellular pathogen Legionella pneumophila interferes with autophagy by delivering an effector protein, RavZ, into the host cytosol. RavZ acts by cleaving membrane-conjugated Atg8/LC3 proteins from pre-autophagosomal structures. Its remarkable efficiency allows minute quantities of RavZ to block autophagy throughout the cell. To understand how RavZ targets pre-autophagosomes and specifically acts only on membrane-associated Atg8 proteins, we elucidated its structure. Revealed is a catalytic domain related in fold to Ulp family deubiquitinase-like enzymes and a C-terminal PI3P-binding module. RavZ targets the autophagosome via the PI3P-binding module and a catalytic domain helix, and it preferentially binds high-curvature membranes, intimating localization to highly curved domains in autophagosome intermediate membranes. RavZ-membrane interactions enhance substrate affinity, providing a mechanism for interfacial activation that also may be used by host autophagy proteins engaging only lipidated Atg8 proteins. |
| Databáze: | OpenAIRE |
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