The 1:2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane
| Autor: | Woo Cheol Lee, Leehyeon Kim, Byeong Won Kim, Hyun Kyu Song, Kwang Yeon Hwang, Sulhee Kim, Ju Han Song, Do Hoon Kwon, Yang Ouk Jung, In Young Lee, Seung Beom Hong, Eui Ju Choi, Kyung Hye Roh |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Autophagy-Related Proteins Legionella Crystallography X-Ray Bioinformatics Legionella pneumophila 03 medical and health sciences Bacterial Proteins Protein Domains Catalytic Domain Phagosomes Autophagy Xenophagy Humans Scattering Radiation Molecular Biology Phagocytes biology Mechanism (biology) Effector Active site Cell Biology Surface Plasmon Resonance biology.organism_classification Basic Research Paper Cell biology Cysteine Endopeptidases HEK293 Cells 030104 developmental biology embryonic structures biology.protein biological phenomena cell phenomena and immunity Microtubule-Associated Proteins Bacteria Function (biology) Protein Binding |
| DOI: | 10.6084/m9.figshare.4123173 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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