9TMK

Structure of CYLD CAP-Gly2 bound to Listeria effector protein InlC

Summary for 9TMK

• Entry DOI: 10.2210/pdb9tmk/pdb
• Descriptor: Internalin C, Ubiquitin carboxyl-terminal hydrolase CYLD, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: effector protein, deubiquitinating, ubiquitin, immune system
• Biological source: Listeria monocytogenes; More
• Total number of polymer chains: 2
• Total formula weight: 39566.93

Authors

Ellison, C.J.,Elliott, P.R. (deposition date: 2025-12-14, release date: 2026-09-30, Last modification date: 2026-10-14)

Primary citation

Ammendolia, D.A.,Ellison, C.J.,Zheng, Y.,Coyaud, E.,Laurent, E.M.N.,Yan, B.R.,Manning, B.,Waldmann, A.K.,Tan, J.M.J.,Frendo-Cumbo, S.,Lyons, C.,Youn, J.Y.,Raught, B.,Ireton, K.,Higgins, D.E.,Elliott, P.R.,Brumell, J.H.
Listeria promotes systemic infection by targeting the host deubiquitinase CYLD.
Nat Commun, 17:-, 2026

PubMed Abstract: Listeria monocytogenes (Lm) is an intracellular pathogen that can cause life-threatening systemic infections. Internalin C (InlC) is a secreted factor required for full Lm virulence in systemic models of infection by mechanisms that remain unclear. Here, we show that InlC binds to CYLD, a host deubiquitinase and regulator of innate immunity. Structurally, we reveal the LRR domain of InlC binds the CAP-Gly2 domain of CYLD, independently of InlC's binding site for other host target proteins. Lm strains harboring amino acid substitutions in InlC that selectively disrupt binding to CYLD were examined. We demonstrate that after Lm accesses the host cytosol, InlC recruits CYLD to ubiquitin-positive bacteria. Recruitment of CYLD was dependent on the host E3 ligase RNF213, a major initiator of ubiquitin-mediated defenses. Furthermore, InlC-CYLD binding contributed to Lm virulence in mice. Together, these findings reveal how a secreted bacterial factor promotes the recruitment of a host deubiquitinase to cytosolic bacteria in response to ubiquitin-mediated defenses.

PubMed: 42811002
DOI: 10.1038/s41467-026-77063-5

Experimental method

X-RAY DIFFRACTION (1.8 Å)