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| Item Type: | Preprint |
|---|---|
| Title: | Structural basis for membrane targeting and secretion of legionella SidE ubiquitin ligases |
| Creators: |
Misra, Mohit  ORCID: https://orcid.org/0000-0001-6309-8066, Mukherjee, Rukmini, Bhattacharya, Anshu, Weng, Tsai-Hsuan ORCID: https://orcid.org/0000-0002-3708-6384, Li, Chuang, Chen, Wenbo, van Ek, Larissa ORCID: https://orcid.org/0000-0002-8047-1560, Mohammed, Ahmed, Cristiani, Alberto, Liu, Yaobin, Pomirska, Julia, Vidov, Adela, Grewe, Diana, van der Heden van Noort, Gerbrand ORCID: https://orcid.org/0000-0001-5955-6431, Hummer, Gerhard ORCID: https://orcid.org/0000-0001-7768-746X, Gavin, Anne-Claude ORCID: https://orcid.org/0000-0003-4917-2340, Safarian, Schara, Luo, Zhao-Qing ORCID: https://orcid.org/0000-0001-8890-6621, Bhaskara, Ramachandra ORCID: https://orcid.org/0000-0002-7742-0391, Svergun, Dmitri, Kudryashev, Misha ORCID: https://orcid.org/0000-0003-3550-6274 and Dikic, Ivan ORCID: https://orcid.org/0000-0001-8156-9511
|
| Abstract: | SidE family effectors from Legionella pneumophila catalyze serine ubiquitination of host proteins via phospho-ribose (PR) linkages, disrupting host compartments, facilitating the formation of Legionella-containing vacuoles (LCVs) and blocking xenophagy. Upon infection, SidE proteins are injected into the cytosol and recruited to host membranes. Here we present structural and functional insights into a previously uncharacterized C-terminal domain (CTD) of SidE effectors. The crystal structure reveals a banana-shape resembling eukaryotic BAR-domain dimers, with an amphipathic helix and electropositive patch mediating membrane association. Membrane targeting to ER and Golgi confers substrate specificity for PR-ubiquitination. We further show that the CTD binds the IcmS-IcmW-DotL complex, acting as a secretion signal for the Type IV secretion system. Our findings establish membrane localization and secretion as critical determinants of SidE effector function during Legionella infection. |
| Keywords: | LCV (Legionella containing vacuole), CTD (C-terminal domain), BAR (Bin-amphiphysin-RvS), PR-ubiquitination (Phospho-ribose ubiquitination), DUB (DeUBiquitinase), PDE (Phosphodiesterase), mART (mono-ADP-ribosyl transferase), CC (Coiled coil), T4SS (Type IV secretion system) |
| Source: | Research Square |
| Publisher: | Research Square |
| Article Number: | rs.3.rs-6524297/v1 |
| Date: | 12 May 2025 |
| Official Publication: | https://doi.org/10.21203/rs.3.rs-6524297/v1 |
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