8X4J

Crystal structure of the glycosyltransferase domain of Legionella SetA (unbound)

Summary for 8X4J

• Entry DOI: 10.2210/pdb8x4j/pdb
• Descriptor: Subversion of eukaryotic traffic protein A, MAGNESIUM ION (3 entities in total)
• Functional Keywords: glycosyltransferase activity, transferase
• Biological source: Legionella pneumophila
• Total number of polymer chains: 1
• Total formula weight: 53811.26

Authors

Im, H.N.,Lee, Y.,Jang, D.M.,Hahn, H.,Kim, H.S. (deposition date: 2023-11-15, release date: 2025-02-19, Last modification date: 2026-04-08)

Primary citation

Im, H.N.,Lee, Y.,Song, Y.,Hahn, H.,Jeon, H.,Shin, D.,Lee, S.,Kim, K.H.,Kim, K.T.,Suh, S.W.,Jang, D.M.,Kim, H.S.
Structural insights into SetA-mediated Rab1 glucosylation and PI3P-guided localization during early Legionella infection.
Proc.Natl.Acad.Sci.USA, 123:e2535016123-e2535016123, 2026

PubMed Abstract: The bacterial pathogen secretes effector proteins that remodel host endomembranes to establish a replication-permissive niche known as the -containing vacuole (LCV). Among these, SetA disrupts vesicle trafficking by glucosylating the small GTPase Rab1, essential for ER-to-Golgi transport. Here, we report comprehensive structural and mechanistic insights into SetA-mediated Rab1 glucosylation and its PI3P-dependent membrane targeting. Crystal structures of its N-terminal glycosyltransferase and C-terminal lipid-binding domains, captured in multiple ligand-bound states, reveal how SetA specifically recognizes GDP-bound Rab1 and the head group of phosphatidylinositol 3-phosphate (PI3P), which is enriched on early LCV membranes. SAXS-based full-length modeling, biochemical assays, and cellular imaging analyses demonstrate that SetA integrates Rab1 modification with membrane localization, thereby perturbing Golgi integrity and ER morphology. Together, these findings define the dual structural mechanisms underlying SetA's coordination of substrate glucosylation and membrane association, providing a spatiotemporal framework for understanding 's early infection strategy.

PubMed: 41894332
DOI: 10.1073/pnas.2535016123

Experimental method

X-RAY DIFFRACTION (2.54 Å)