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| Title | Structural basis of specific lysine transport by Pseudomonas aeruginosa permease LysP. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 17, Issue 1, Page 37, Year 2025 |
| Publish date | Dec 4, 2025 |
Authors | Deniz Bicer / Rei Matsuoka / Aurélien F A Moumbock / Preethi Sukumar / Albert Suades / Harish Cheruvara / Andrew Quigley / David Drew / Els Pardon / Jan Steyaert / Peter J F Henderson / Martin Caffrey / Julia J Griese / Emmanuel Nji / ![]() |
| PubMed Abstract | Under conditions of extreme acidity, the lysine-specific permease, LysP, not only mediates the import of L-lysine it also interacts with the transcriptional regulator, CadC, to activate expression of ...Under conditions of extreme acidity, the lysine-specific permease, LysP, not only mediates the import of L-lysine it also interacts with the transcriptional regulator, CadC, to activate expression of the cadAB operon. This operon encodes the lysine decarboxylase, CadA, which converts lysine to cadaverine while consuming a cytoplasmic proton, and the antiporter, CadB, which exports protonated cadaverine in exchange for extracellular lysine. Together, these processes contribute to cytoplasmic pH homeostasis and support bacterial acid resistance - a mechanism essential for the survival of pathogenic bacteria in acidic host environments. Here, we present the cryo-EM structure of LysP from Pseudomonas aeruginosa in an inward-occluded conformation (3.2-5.3 Å resolution), bound to L-lysine and a nanobody. L-Lysine is coordinated by hydrophobic contacts, cation-π interactions, and by hydrogen bonding mostly with polar uncharged residues. Reconstitution of LysP into proteoliposomes confirms specific L-lysine transport, which is competitively inhibited by L-4-thialysine. These findings provide a structural framework for understanding selective lysine recognition and inhibition, with implications for antibacterial drug design. |
External links | Nat Commun / PubMed:41345107 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.68 Å |
| Structure data | EMDB-50053, PDB-9eyd: |
| Chemicals | ![]() ChemComp-LYS: |
| Source |
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Keywords | MEMBRANE PROTEIN / Complex |
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pseudomonas aeruginosa pao1 (bacteria)
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