BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

LIR motifs and the membrane-targeting domain are complementary in the function of RavZ

  • Park, Sang-Won (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Jun, Yong-Woo (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Jeon, Pureum (Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University) ;
  • Lee, You-Kyung (Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University) ;
  • Park, Ju-Hui (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Lee, Seung-Hwan (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Lee, Jin-A (Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University) ;
  • Jang, Deok-Jin (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University)
  • Received : 2019.08.19
  • Accepted : 2019.10.17
  • Published : 2019.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

The bacterial effector protein RavZ is secreted by the intracellular pathogen Legionella pneumophila and inhibits host autophagy through an irreversible deconjugation of mammalian ATG8 (mATG8) proteins from autophagosome membranes. However, the roles of the LC3 interacting region (LIR) motifs in RavZ function remain unclear. In this study, we show that a membrane-targeting (MT) domain or the LIR motifs of RavZ play major or minor roles in RavZ function. A RavZ mutant that does not bind to mATG8 delipidated all forms of mATG8-phosphatidylethanolamine (PE) as efficiently as did wild-type RavZ. However, a RavZ mutant with a deletion of the MT domain selectively delipidated mATG8-PE less efficiently than did wild-type RavZ. Taken together, our results suggest that the effects of LIR motifs and the MT domain on RavZ activity are complementary and work through independent pathways.

Keywords

References

  1. Levine B and Kroemer G (2019) Biological Functions of Autophagy Genes: A Disease Perspective. Cell 176, 11-42 https://doi.org/10.1016/j.cell.2018.09.048
  2. Slobodkin MR and Elazar Z (2013) The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy. Essays Biochem 55, 51-64 https://doi.org/10.1042/bse0550051
  3. Lee YK and Lee JA (2016) Role of the Mammalian ATG8/LC3 Family in Autophagy: Differential and Compensatory Roles in the Spatiotemporal Regulation of Autophagy. BMB Rep 49, 424-430 https://doi.org/10.5483/BMBRep.2016.49.8.081
  4. Gatica D, Lahiri V and Klionsky DJ (2018) Cargo recognition and degradation by selective autophagy. Nat Cell Biol 20, 233-242 https://doi.org/10.1038/s41556-018-0037-z
  5. Um JH and Yun J (2017) Emerging role of mitophagy in human diseases and physiology. BMB Rep 50, 299-307 https://doi.org/10.5483/BMBRep.2017.50.6.056
  6. Sharma V, Verma S, Seranova E, Sarkar S and Kumar D (2018) Selective Autophagy and Xenophagy in Infection and Disease. Front Cell Dev Biol 6, 147 https://doi.org/10.3389/fcell.2018.00147
  7. Kwon DH and Song HK (2018) A Structural View of Xenophagy, a Battle between Host and Microbes. Mol Cells 41, 27-34 https://doi.org/10.14348/MOLCELLS.2018.2274
  8. Sherwood RK and Roy CR (2016) Autophagy Evasion and Endoplasmic Reticulum Subversion: The Yin and Yang of Legionella Intracellular Infection. Annu Rev Microbiol 70, 413-433 https://doi.org/10.1146/annurev-micro-102215-095557
  9. Choy A, Dancourt J, Mugo B et al (2012) The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science 338, 1072-1076 https://doi.org/10.1126/science.1227026
  10. Horenkamp FA, Kauffman KJ, Kohler LJ et al (2015) The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Dev Cell 34, 569-576 https://doi.org/10.1016/j.devcel.2015.08.010
  11. Yang A and Pantoom S (2017) Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins. Elife 6, e23905 https://doi.org/10.7554/eLife.23905
  12. Skytte Rasmussen M, Mouilleron S, Kumar Shrestha B et al (2017) ATG4B contains a C-terminal LIR motif important for binding and efficient cleavage of mammalian orthologs of yeast Atg8. Autophagy 13, 834-853 https://doi.org/10.1080/15548627.2017.1287651
  13. Kauffman KJ, Yu S, Jin J et al (2018) Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases. Autophagy 14, 992-1010
  14. Abreu S, Kriegenburg F and Gomez-Sanchez R (2017) Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation. EMBO Rep 18, 765-780 https://doi.org/10.15252/embr.201643146
  15. Kwon DH, Kim S, Jung YO et al (2017) The 1:2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane. Autophagy 13, 70-81 https://doi.org/10.1080/15548627.2016.1243199
  16. Nascimbeni AC, Codogno P and Morel E (2017) Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics. FEBS J 284, 1267-1278 https://doi.org/10.1111/febs.13987
  17. Jang DJ and Lee JA (2016) The roles of phosphoinositides in mammalian autophagy. Arch Pharm Res 39, 1129-1136 https://doi.org/10.1007/s12272-016-0777-x
  18. Carlsson SR and Simonsen A (2015) Membrane dynamics in autophagosome biogenesis. J Cell Sci 128, 193-205 https://doi.org/10.1242/jcs.141036
  19. Pantoom S, Yang A and Wu YW (2017) Lift and cut: Anti-host autophagy mechanism of Legionella pneumophila. Autophagy 13, 1467-1469 https://doi.org/10.1080/15548627.2017.1327943
  20. Lee YK, Jun YW, Choi HE et al (2017) Development of LC3/GABARAP sensors containing a LIR and a hydrophobic domain to monitor autophagy. EMBO J 36, 1100-1116 https://doi.org/10.15252/embj.201696315
  21. Park SW, Jun YW, Choi HE, Lee JA and Jang DJ (2019) Deciphering the molecular mechanisms underlying the plasma membrane targeting of PRMT8. BMB Rep 52, 601-606 https://doi.org/10.5483/BMBRep.2019.52.10.272