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TitleStructural basis of specific lysine transport by Pseudomonas aeruginosa permease LysP.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Page 37, Year 2025
Publish dateDec 4, 2025
AuthorsDeniz 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 AbstractUnder 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 linksNat Commun / PubMed:41345107 / PubMed Central
MethodsEM (single particle)
Resolution3.68 Å
Structure data

EMDB-50053, PDB-9eyd:
Structural basis of specific lysine transport by Pseudomonas aeruginosa permease LysP
Method: EM (single particle) / Resolution: 3.68 Å

Chemicals

ChemComp-LYS:
LYSINE

Source
  • pseudomonas aeruginosa pao1 (bacteria)
  • lama glama (llama)
KeywordsMEMBRANE PROTEIN / Complex

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