PXD069660-1

PXD069660 is an original dataset announced via ProteomeXchange.

Title	Structural snapshots of Pseudomonas aeruginosa LptB2FG and LptB2FGC reveal insights into lipopolysaccharide recognition and transport - native mass spectrometry data
Description	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 LptB2FGC 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 LptB2FG and LptB2FGC, 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.
HostingRepository	PRIDE
AnnounceDate	2025-10-22
AnnouncementXML	Submission_2025-10-21_20:42:57.009.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Francesco Fiorentino
SpeciesList	scientific name: Pseudomonas aeruginosa PAO1; NCBI TaxID: NEWT:208964;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive UHMR

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-20 02:59:31	ID requested
⏵ 1	2025-10-21 20:42:57	announced

Dataset with its publication pending

submitter keyword: lipopolysaccharide, LPS, native MS, LptB2FG,P. aeruginosa, LptB2FGC

Francesco Fiorentino
contact affiliation	Sapienza University of Rome
contact email	f.fiorentino@uniroma1.it
lab head
Francesco Fiorentino
contact affiliation	Sapienza University of Rome
contact email	f.fiorentino@uniroma1.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069660
     1. Label: PRIDE project
     2. Name: Structural snapshots of Pseudomonas aeruginosa LptB2FG and LptB2FGC reveal insights into lipopolysaccharide recognition and transport - native mass spectrometry data