5ODW

Structure of the FpvAI-pyocin S2 complex

Summary for 5ODW

• Entry DOI: 10.2210/pdb5odw/pdb
• Descriptor: Ferripyoverdine receptor, Pyocin-S2, SULFATE ION (3 entities in total)
• Functional Keywords: antimicrobial protein, membrane protein complex, protein transport
• Biological source: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1); More
• Cellular location: Cell outer membrane: P48632
• Total number of polymer chains: 4
• Total formula weight: 232052.79

Authors

White, P.,Joshi, A.,Kleanthous, C. (deposition date: 2017-07-06, release date: 2017-11-08, Last modification date: 2024-01-17)

Primary citation

White, P.,Joshi, A.,Rassam, P.,Housden, N.G.,Kaminska, R.,Goult, J.D.,Redfield, C.,McCaughey, L.C.,Walker, D.,Mohammed, S.,Kleanthous, C.
Exploitation of an iron transporter for bacterial protein antibiotic import.
Proc. Natl. Acad. Sci. U.S.A., 114:12051-12056, 2017

PubMed Abstract: Unlike their descendants, mitochondria and plastids, bacteria do not have dedicated protein import systems. However, paradoxically, import of protein bacteriocins, the mechanisms of which are poorly understood, underpins competition among pathogenic and commensal bacteria alike. Here, using X-ray crystallography, isothermal titration calorimetry, confocal fluorescence microscopy, and in vivo photoactivatable cross-linking of stalled translocation intermediates, we demonstrate how the iron transporter FpvAI in the opportunistic pathogen is hijacked to translocate the bacteriocin pyocin S2 (pyoS2) across the outer membrane (OM). FpvAI is a TonB-dependent transporter (TBDT) that actively imports the small siderophore ferripyoverdine (Fe-Pvd) by coupling to the proton motive force (PMF) via the inner membrane (IM) protein TonB1. The crystal structure of the N-terminal domain of pyoS2 (pyoS2) bound to FpvAI ( = 240 pM) reveals that the pyocin mimics Fe-Pvd, inducing the same conformational changes in the receptor. Mimicry leads to fluorescently labeled pyoS2 being imported into FpvAI-expressing cells by a process analogous to that used by bona fide TBDT ligands. PyoS2 induces unfolding by TonB1 of a force-labile portion of the plug domain that normally occludes the central channel of FpvAI. The pyocin is then dragged through this narrow channel following delivery of its own TonB1-binding epitope to the periplasm. Hence, energized nutrient transporters in bacteria also serve as rudimentary protein import systems, which, in the case of FpvAI, results in a protein antibiotic 60-fold bigger than the transporter's natural substrate being translocated across the OM.

PubMed: 29078392
DOI: 10.1073/pnas.1713741114

Experimental method

X-RAY DIFFRACTION (2.8 Å)