9DOK
Cryo-EM structure of LptB2FG apo-II
Summary for 9DOK
| Entry DOI | 10.2210/pdb9dok/pdb |
| EMDB information | 47085 |
| Descriptor | Lipopolysaccharide export system ATP-binding protein LptB, Permease, Lipopolysaccharide export system permease protein LptF, ... (4 entities in total) |
| Functional Keywords | lps transporter, lipid transport |
| Biological source | Pseudomonas aeruginosa More |
| Total number of polymer chains | 4 |
| Total formula weight | 139815.02 |
| Authors | Su, C.C. (deposition date: 2024-09-19, release date: 2025-11-19, Last modification date: 2025-12-31) |
| Primary citation | Fiorentino, F.,Cervoni, M.,Wang, Y.,Urner, L.H.,Sauer, J.B.,Tran, A.,Corey, R.A.,Rotili, D.,Mai, A.,Stansfeld, P.J.,Imperi, F.,Yu, E.W.,Su, C.C.,Robinson, C.V.,Bolla, J.R. Structural snapshots of Pseudomonas aeruginosa LptB 2 FG and LptB 2 FGC reveal insights into lipopolysaccharide recognition and transport. Nat Commun, 16:11384-11384, 2025 Cited by PubMed Abstract: Gram-negative bacteria are intrinsically resistant to many antibiotics because of densely packed lipopolysaccharides (LPS) in the outer leaflet of their outer membrane (OM), which acts as a highly effective barrier towards the spontaneous permeation of toxic molecules, including antibiotics. LPS are extracted from the inner membrane by the ABC transporter LptBFGC and translocated across the periplasm via a protein bridge to the OM. While structural studies have elucidated aspects of Lpt function in enterobacteria, little is known about how this system operates in divergent species such as Pseudomonas aeruginosa, a major human pathogen. Here, we report five cryo-electron microscopy structures of P. aeruginosa LptBFG and LptBFGC, revealing a rigid body movement in the periplasmic β-jellyroll domains necessary for LPS to shuttle through the periplasmic space. Notably, these structures exhibit a significantly smaller LPS binding cavity compared to previously determined models, suggesting the ligand-unbound states of the transporter. Mass spectrometry and molecular dynamics simulations indicate that the phosphate groups of LPS are the key determinants for binding and that the transporter can also accommodate cardiolipin. Together, these findings reveal previously unappreciated structural diversity in the Lpt system and provide mechanistic insight into how pathogenic Gram-negative bacteria tailor LPS recognition and transport. This understanding offers new avenues for the development of novel inhibitors targeting membrane biogenesis. PubMed: 41407669DOI: 10.1038/s41467-025-66182-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.26 Å) |
Structure validation
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