The structural basis of promiscuity in small multidrug resistance transporters.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33247110.
- Also identified by DOI 10.1038/s41467-020-19820-8 and PMC identifier 7695847.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
By providing broad resistance to environmental biocides, transporters from the small multidrug resistance (SMR) family drive the spread of multidrug resistance cassettes among bacterial populations. A fundamental understanding of substrate selectivity by SMR transporters is needed to identify the types of selective pressures that contribute to this process. Using solid-supported membrane electrophysiology, we find that promiscuous transport of hydrophobic substituted cations is a general feature of SMR transporters. To understand the molecular basis for promiscuity, we solved X-ray crystal structures of a SMR transporter Gdx-Clo in complex with substrates to a maximum resolution of 2.3 Å. These structures confirm the family's extremely rare dual topology architecture and reveal a cleft between two helices that provides accommodation in the membrane for the hydrophobic substituents of transported drug-like cations.
Medical subject headings
- Bacterial Proteins
- Drug Resistance, Multiple, Bacterial
- Membrane Transport Proteins