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 Communjournal_title
Nature communicationsauthors
Kermani AA,Macdonald CB,Burata OE,Ben Koff B,Koide A,Denbaum E,Koide S,Stockbridge RBdoi
10.1038/s41467-020-19820-8subject
Has Abstractpub_date
2020-11-27 00:00:00pages
6064issue
1issn
2041-1723pii
10.1038/s41467-020-19820-8journal_volume
11pub_type
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