The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs

Developmental Cell
Florian A HorenkampKarin M Reinisch

Abstract

Autophagy 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.

References

Mar 19, 2005·The EMBO Journal·Lin-nan ShenRonald T Hay
Sep 27, 2005·The Journal of Biological Chemistry·Kenji SugawaraFuyuhiko Inagaki
Oct 3, 2007·Nature Cell Biology·Zhiping Xie, Daniel J Klionsky
Nov 10, 2009·Nature Cell Biology·Mitsuko Hayashi-NishinoAkitsugu Yamamoto
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Aug 18, 2010·Chembiochem : a European Journal of Chemical Biology·Peixiang MaDieter Willbold
Oct 1, 2010·Cellular Microbiology·Li HuangRalph R Isberg
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Weiliang FanQing Zhong
Mar 28, 2012·Annual Review of Immunology·Petric KuballaRamnik J Xavier
Jan 12, 2013·Current Biology : CB·Claudia Dall'ArmiGilbert Di Paolo
Dec 25, 2013·Cell Research·Yuchen FengDaniel J Klionsky
Jan 5, 2014·Nature Reviews. Microbiology·Ju Huang, John H Brumell

❮ Previous
Next ❯

Citations

Feb 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Monica RolandoCarmen Buchrieser
Feb 26, 2016·ELife·Paul de Figueiredo, Marty Dickman
Sep 9, 2016·Annual Review of Microbiology·Racquel Kim Sherwood, Craig R Roy
Dec 17, 2016·Current Opinion in Microbiology·Lara J Kohler, Craig R Roy
Dec 16, 2016·The FEBS Journal·Anna Chiara NascimbeniEtienne Morel
Mar 30, 2018·FEMS Microbiology Reviews·Eric MartinezMatteo Bonazzi
May 12, 2018·Autophagy·Katarzyna Zientara-Rytter, Suresh Subramani
Nov 4, 2017·The Journal of Cell Biology·Elias CornejoShaeri Mukherjee
Dec 14, 2017·Essays in Biochemistry·David G McEwan
Dec 24, 2018·The Journal of Biological Chemistry·Nadezhda LevanovaGunnar Neels Schroeder
Sep 14, 2017·The Journal of Antibiotics·Tatsuro Maruyama, Nobuo N Noda
Nov 14, 2019·Scientific Reports·Sang-Won ParkDeok-Jin Jang
Jul 21, 2020·Chembiochem : a European Journal of Chemical Biology·Aimin YangYao-Wen Wu
Jul 29, 2020·Cellular Microbiology·Anna Leoni SwartHubert Hilbi
Aug 28, 2020·PLoS Pathogens·Igor TascónMatthias P Machner
Jul 9, 2016·FEBS Letters·Alf Håkon Lystad, Anne Simonsen
Jun 8, 2018·Frontiers in Immunology·Mariana da Silva SiqueiraLeonardo H Travassos
Aug 22, 2018·Cells·Anne-Claire JacominMarie-Odile Fauvarque
May 29, 2020·Journal of Cell Science·Yingying CongFulvio Reggiori
Oct 4, 2017·Frontiers in Cellular and Infection Microbiology·Tomoko KuboriHiroki Nagai
Mar 3, 2020·Frontiers in Immunology·A Leoni Swart, Hubert Hilbi
Feb 21, 2018·Autophagy·Karlina J KauffmanThomas J Melia
Dec 31, 2020·Proceedings of the National Academy of Sciences of the United States of America·Zhike FengPeter D Nagy
Oct 24, 2020·Trends in Microbiology·Ligang MeiAimin Yang
Dec 1, 2020·Frontiers in Cellular and Infection Microbiology·David R ThomasHayley J Newton
Apr 3, 2020·Current Opinion in Cell Biology·Julia Noack, Shaeri Mukherjee
Mar 3, 2021·The FEBS Journal·Andrey GrishinMiroslaw Cygler
Apr 4, 2021·Microorganisms·Vera VozandychovaJiri Stulik
Apr 27, 2019·Microbiology Spectrum·Titilayo O Omotade, Craig R Roy
Aug 6, 2021·Expert Review of Proteomics·Michael Overduin, Troy A Kervin

❮ Previous
Next ❯

Related Concepts

Related Feeds

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Related Papers

Seikagaku. The Journal of Japanese Biochemical Society
Kuninori Suzuki, Yoshinori Ohsumi
The Annals of Occupational Hygiene
J B Kurtz
Nihon rinsho. Japanese journal of clinical medicine
K Izumikawa, S Kohno
© 2021 Meta ULC. All rights reserved