The structural basis of promiscuity in small multidrug resistance transporters.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Kermani AA,Macdonald CB,Burata OE,Ben Koff B,Koide A,Denbaum E,Koide S,Stockbridge RB

doi

10.1038/s41467-020-19820-8

subject

Has Abstract

pub_date

2020-11-27 00:00:00

pages

6064

issue

1

issn

2041-1723

pii

10.1038/s41467-020-19820-8

journal_volume

11

pub_type

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