Year: 2025
Type: preprint
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.
Source: Research Square
Authors: Ivan Dikic, Mohit Misra, Rukmini Mukherjee, Anshu Bhattacharya, Tsai-Hsuan Weng, Chuang Li, Wenbo Chen, Larissa van Ek, Ahmed Mohammed, Alberto Cristiani, Yaobin Liu, Julia Pomirska, Adela Vidov, Diana Grewe, Gerbrand van der Heden van Noort, Gerhard Hummer, Anne-Claude Gavin, Schara Safarian, Zhao-Qing Luo, Ramachandra Bhaskara, Dmitri Svergun, Misha Kudryashev
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4410334046