6T1Z

LmrP from L. lactis, in an outward-open conformation, bound to Hoechst 33342

Summary for 6T1Z

• Entry DOI: 10.2210/pdb6t1z/pdb
• Descriptor: LmrP integral membrane protein, 2'-(4-ETHOXYPHENYL)-5-(4-METHYL-1-PIPERAZINYL)-2,5'-BI-BENZIMIDAZOLE, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHATE, ... (6 entities in total)
• Functional Keywords: transmembrane multidrug transporter, transport protein
• Biological source: Lactococcus lactis
• Total number of polymer chains: 1
• Total formula weight: 48026.93

Authors

Hutchin, A.,Debruycker, V.,Masureel, M.,Legrand, P.,Remaut, H.,Govaerts, C. (deposition date: 2019-10-07, release date: 2020-07-29, Last modification date: 2024-05-01)

Primary citation

Debruycker, V.,Hutchin, A.,Masureel, M.,Ficici, E.,Martens, C.,Legrand, P.,Stein, R.A.,Mchaourab, H.S.,Faraldo-Gomez, J.D.,Remaut, H.,Govaerts, C.
An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity.
Nat.Struct.Mol.Biol., 27:829-835, 2020

PubMed Abstract: Multidrug efflux pumps present a challenge to the treatment of bacterial infections, making it vitally important to understand their mechanism of action. Here, we investigate the nature of substrate binding within Lactococcus lactis LmrP, a prototypical multidrug transporter of the major facilitator superfamily. We determined the crystal structure of LmrP in a ligand-bound outward-open state and observed an embedded lipid in the binding cavity of LmrP, an observation supported by native mass spectrometry analyses. Molecular dynamics simulations suggest that the anionic lipid stabilizes the observed ligand-bound structure. Mutants engineered to disrupt binding of the embedded lipid display reduced transport of some, but not all, antibiotic substrates. Our results suggest that a lipid within the binding cavity could provide a malleable hydrophobic component that allows adaptation to the presence of different substrates, helping to explain the broad specificity of this protein and possibly other multidrug transporters.

PubMed: 32719456
DOI: 10.1038/s41594-020-0464-y

Experimental method

X-RAY DIFFRACTION (2.9 Å)