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 journalArticle

15 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)1-12
Number of pages12
JournalAutophagy
DOIs
Publication statusAccepted/In press - 2016 Nov 18

Fingerprint

Autophagy
Membranes
Bacteria
Legionella pneumophila
Catalytic Domain
Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The 1 : 2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane. / Kwon, Do Hoon; Kim, Sulhee; Jung, Yang Ouk; Roh, Kyung Hye; Kim, Leehyeon; Kim, Byeong Won; Hong, Seung Beom; Lee, In Young; Song, Ju Han; Lee, Woo Cheol; Choi, Eui Ju; Hwang, Kwang Yeon; Song, Hyun Kyu.

In: Autophagy, 18.11.2016, p. 1-12.

Research output: Contribution to journalArticle

Kwon, Do Hoon ; Kim, Sulhee ; Jung, Yang Ouk ; Roh, Kyung Hye ; Kim, Leehyeon ; Kim, Byeong Won ; Hong, Seung Beom ; Lee, In Young ; Song, Ju Han ; Lee, Woo Cheol ; Choi, Eui Ju ; Hwang, Kwang Yeon ; Song, Hyun Kyu. / The 1 : 2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane. In: Autophagy. 2016 ; pp. 1-12.
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