Characterization of the molecular mechanism of the autophagy-related Atg8-Atg3 protein interaction in Toxoplasma gondii

The Journal of Biological Chemistry
Shuxian LiuFeng Tan

Abstract

Toxoplasmosis is caused by an obligate intracellular parasite, the protozoan Toxoplasma gondii Discovery of novel drugs against T. gondii infection could circumvent the toxicity of existing drugs and T. gondii resistance to current treatments. The autophagy-related protein 8 (Atg8)-Atg3 interaction in T. gondii is a promising drug target because of its importance for regulating Atg8 lipidation. We reported previously that TgAtg8 and TgAtg3 interact directly. Here we validated that substitutions of conserved residues of TgAtg8 interacting with the Atg8 family-interacting motif (AIM) in Atg3 disrupt the TgAtg8-TgAtg3 interaction and reduce TgAtg8 lipidation and autophagosome formation. These findings were consistent with results reported previously for Plasmodium Atg8, suggesting functional conservation of Atg8 in Toxoplasma and Plasmodium. Moreover, using peptide and AlphaScreen assays, we identified the AIM sequence in TgAtg3 that binds TgAtg8. We determined that the core TgAtg3 AIM contains a Phe239-Ala240-Asp241-Ile242 (239FADI242) signature distinct from the 105WLLP108 signature in the AIM of Plasmodium Atg3. Furthermore, an alanine-scanning assay revealed that the TgAtg8-TgAtg3 interaction in T. gondii also depends strongly...Continue Reading

References

Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·E F UllmanC N Skold
May 8, 1999·Molecular Biology of the Cell·I TanidaE Kominami
Dec 2, 2000·Nature·Y IchimuraY Ohsumi
Oct 6, 2001·Trends in Parasitology·C G LüderD Soldati
Jul 22, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kenji SugawaraFuyuhiko Inagaki
Nov 22, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Nobuo N NodaFuyuhiko Inagaki
Feb 17, 2009·International Journal for Parasitology·Louis M Weiss, Jitender P Dubey
Jan 20, 2010·FEBS Letters·Nobuo N NodaFuyuhiko Inagaki
Dec 4, 2010·Parasites & Vectors·Carsten Gk LüderGer van Zandbergen
Dec 30, 2010·Autophagy·Terje Johansen, Trond Lamark
Apr 26, 2011·Cancer Research·Rachel C BrennanMichael A Dyer
May 10, 2011·Annual Review of Biochemistry·Hilla WeidbergZvulun Elazar
Nov 19, 2011·FEMS Microbiology Reviews·William J Sullivan, Victoria Jeffers
Dec 17, 2011·PLoS Pathogens·Sarah E ReeceAndy Gardner
Jan 4, 2012·Cellular Microbiology·Debasish GhoshAnthony P Sinai
Apr 13, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Charles M RudinLeena Gandhi
Apr 21, 2012·Molecular and Biochemical Parasitology·Sébastien Besteiro
Jul 24, 2012·Trends in Parasitology·Anthony P Sinai, Paul D Roepe
Aug 18, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M A DicksonG K Schwartz
Sep 18, 2012·Journal of Structural Biology·Adelaide U P HainJürgen Bosch
Jun 12, 2013·Autophagy·Marie A Kong-HapSébastien Besteiro
Sep 13, 2013·Autophagy·Andrew M TomlinsGordon Langsley
Sep 28, 2013·Essays in Biochemistry·Moran Rawet Slobodkin, Zvulun Elazar
Apr 15, 2014·Cell·James H Hurley, Brenda A Schulman
May 31, 2014·Nature Cell Biology·Alexandra StolzIvan Dikic
Sep 6, 2014·Parasites & Vectors·William Alberto Cañón-FrancoJitender P Dubey
Sep 27, 2015·Acta Tropica·Di ChenFeng Tan
Apr 17, 2017·Biomedical Journal·Perle Latré de LatéGordon Langsley

❮ Previous
Next ❯

Citations

Sep 26, 2020·Cell & Bioscience·Qian SongBosheng Zhao
Jul 9, 2021·Frontiers in Cell and Developmental Biology·Dongmei FangMin Li

❮ 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

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

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.