The 1:2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane

Do Hoon Kwon, Sulhee Kim, Yang Ouk Jung, Kyung Hye Roh, Leehyeon Kim, Byeong Won Kim, Seung Beom Hong, In Young Lee, Ju Han Song, Woo Cheol Lee, Eui Ju Choi, Kwang Yeon Hwang, Hyun Kyu Song

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Hosts utilize macroautophagy/autophagy to clear invading bacteria; however, bacteria have also developed a specific mechanism to survive by manipulating the host cell autophagy mechanism. One pathogen, Legionella pneumophila, can hinder host cell autophagy by using the specific effector protein RavZ that cleaves phosphatidylethanolamine-conjugated LC3 on the phagophore membrane. However, the detailed molecular mechanisms associated with the function of RavZ have hitherto remained unclear. Here, we report on the biochemical characteristics of the RavZ-LC3 interaction, the solution structure of the 1:2 complex between RavZ and LC3, and crystal structures of RavZ showing different conformations of the active site loop without LC3. Based on our biochemical, structural, and cell-based analyses of RavZ and LC3, both distant flexible N- and C-terminal regions containing LC3-interacting region (LIR) motifs are important for substrate recognition. These results suggest a novel mechanism of RavZ action on the phagophore membrane and lay the groundwork for understanding how bacterial pathogens can survive autophagy.

Original languageEnglish
Pages (from-to)70-81
Number of pages12
JournalAutophagy
Volume13
Issue number1
DOIs
Publication statusPublished - 2017 Jan 2

Bibliographical note

Funding Information:
We thank the staff at beamline 5C, Pohang Accelerator Laboratory, Korea, beamline BL17A, Photon Factory, and beamline BL44XU, Spring-8, Japan for help with the X-ray data collection. We also thank the staff at beamline 4C, Pohang Accelerator Laboratory, Korea, and beamline BL10C, Photon Factory, Japan for help with the SAXS data collection. This work was supported by National Research Foundation of Korea (NRF) grants from the Korean government (BRL grant: No. 2015041919, NRF-2011–0028168 and International Cooperation Program: No. 2015K2A2A6002008) and by the Basic Science Research Program through the NRF, funded by the Ministry of Education (NRF-2013R1A6A3A04063675 to YOJ).

Publisher Copyright:
© 2017 Taylor & Francis.

Keywords

  • ATG4B
  • LC3
  • Legionella pneumophila
  • RavZ
  • SAXS
  • crystal structure
  • xenophagy

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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