7MH6

Structure of EmrE-D3 mutant in complex with monobody L10 in low pH (protonated state)

Summary for 7MH6

• Entry DOI: 10.2210/pdb7mh6/pdb
• Related: 7MGX
• Descriptor: Monobody L10, Multidrug transporter EmrE (3 entities in total)
• Functional Keywords: small multidrug resistance transporter, transport protein-immune system complex, emre, proton bound, transport protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 43480.16

Authors

Kermani, A.A.,Stockbridge, R.B. (deposition date: 2021-04-14, release date: 2022-03-02, Last modification date: 2023-10-18)

Primary citation

Kermani, A.A.,Burata, O.E.,Koff, B.B.,Koide, A.,Koide, S.,Stockbridge, R.B.
Crystal structures of bacterial small multidrug resistance transporter EmrE in complex with structurally diverse substrates.
Elife, 11:-, 2022

PubMed Abstract: Proteins from the bacterial small multidrug resistance (SMR) family are proton-coupled exporters of diverse antiseptics and antimicrobials, including polyaromatic cations and quaternary ammonium compounds. The transport mechanism of the transporter, EmrE, has been studied extensively, but a lack of high-resolution structural information has impeded a structural description of its molecular mechanism. Here, we apply a novel approach, multipurpose crystallization chaperones, to solve several structures of EmrE, including a 2.9 Å structure at low pH without substrate. We report five additional structures in complex with structurally diverse transported substrates, including quaternary phosphonium, quaternary ammonium, and planar polyaromatic compounds. These structures show that binding site tryptophan and glutamate residues adopt different rotamers to conform to disparate structures without requiring major rearrangements of the backbone structure. Structural and functional comparison to Gdx-Clo, an SMR protein that transports a much narrower spectrum of substrates, suggests that in EmrE, a relatively sparse hydrogen bond network among binding site residues permits increased sidechain flexibility.

PubMed: 35254261
DOI: 10.7554/eLife.76766

Experimental method

X-RAY DIFFRACTION (2.85 Å)