title: The 1:2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane.
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.
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Do Hoon
authors: DH
authors: Kwon
authors: b Division of Biotechnology, Korea University , Seongbuk-gu, Seoul , Korea.
authors: Sulhee
authors: S
authors: Kim
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Yang Ouk
authors: YO
authors: Jung
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Kyung-Hye
authors: KH
authors: Roh
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Leehyeon
authors: L
authors: Kim
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Byeong-Won
authors: BW
authors: Kim
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Seung Beom
authors: SB
authors: Hong
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: In Young
authors: IY
authors: Lee
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Ju Han
authors: JH
authors: Song
authors: b Division of Biotechnology, Korea University , Seongbuk-gu, Seoul , Korea.
authors: Woo Cheol
authors: WC
authors: Lee
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Eui-Ju
authors: EJ
authors: Choi
authors: b Division of Biotechnology, Korea University , Seongbuk-gu, Seoul , Korea.
authors: Kwang Yeon
authors: KY
authors: Hwang
authors: a Department of Life Sciences , Korea University , Seongbuk-gu, Seoul , Korea.
authors: Hyun Kyu
authors: HK
authors: Song
mesh_terms: D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007875:Legionella / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008958:Models, Molecular; D010586:Phagocytes / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D012542:Scattering, Radiation; D020349:Surface Plasmon Resonance
chemical_list: D000071183:Autophagy-Related Proteins; D001426:Bacterial Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C507524:ATG4B protein, human; D003546:Cysteine Endopeptidases
keywords: ATG4B; LC3; Legionella pneumophila; RavZ; SAXS; crystal structure; xenophagy