6WXI
Colicin E1 fragment in nanodisc-embedded TolC
Summary for 6WXI
| Entry DOI | 10.2210/pdb6wxi/pdb |
| Related | 6WXH |
| EMDB information | 21959 21960 |
| Descriptor | Outer membrane protein TolC (1 entity in total) |
| Functional Keywords | antibiotic efflux, bacteriocin, transport protein |
| Biological source | Escherichia coli (strain K12) |
| Total number of polymer chains | 3 |
| Total formula weight | 161350.07 |
| Authors | Kaelber, J.T.,Budiardjo, S.J.,Firlar, E.,Ikujuni, A.P.,Slusky, J.S.G. (deposition date: 2020-05-10, release date: 2021-05-12, Last modification date: 2024-05-15) |
| Primary citation | Budiardjo, S.J.,Stevens, J.J.,Calkins, A.L.,Ikujuni, A.P.,Wimalasena, V.K.,Firlar, E.,Case, D.A.,Biteen, J.S.,Kaelber, J.T.,Slusky, J.S.G. Colicin E1 opens its hinge to plug TolC. Elife, 11:-, 2022 Cited by PubMed Abstract: The double membrane architecture of Gram-negative bacteria forms a barrier that is impermeable to most extracellular threats. Bacteriocin proteins evolved to exploit the accessible, surface-exposed proteins embedded in the outer membrane to deliver cytotoxic cargo. Colicin E1 is a bacteriocin produced by, and lethal to, that hijacks the outer membrane proteins (OMPs) TolC and BtuB to enter the cell. Here, we capture the colicin E1 translocation domain inside its membrane receptor, TolC, by high-resolution cryo-electron microscopy to obtain the first reported structure of a bacteriocin bound to TolC. Colicin E1 binds stably to TolC as an open hinge through the TolC pore-an architectural rearrangement from colicin E1's unbound conformation. This binding is stable in live cells as indicated by single-molecule fluorescence microscopy. Finally, colicin E1 fragments binding to TolC plug the channel, inhibiting its native efflux function as an antibiotic efflux pump, and heightening susceptibility to three antibiotic classes. In addition to demonstrating that these protein fragments are useful starting points for developing novel antibiotic potentiators, this method could be expanded to other colicins to inhibit other OMP functions. PubMed: 35199644DOI: 10.7554/eLife.73297 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.84 Å) |
Structure validation
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