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The structural basis of promiscuity in small multidrug resistance transporters.
- Source :
-
Nature communications [Nat Commun] 2020 Nov 27; Vol. 11 (1), pp. 6064. Date of Electronic Publication: 2020 Nov 27. - Publication Year :
- 2020
-
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.
- Subjects :
- Amino Acid Sequence
Bacterial Proteins metabolism
Binding Sites
Biological Transport
Crystallography, X-Ray
Escherichia coli metabolism
Gene Transfer, Horizontal
Guanine metabolism
Hydrophobic and Hydrophilic Interactions
Membrane Transport Proteins metabolism
Models, Molecular
Riboswitch
Substrate Specificity
Bacterial Proteins chemistry
Drug Resistance, Multiple, Bacterial
Membrane Transport Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33247110
- Full Text :
- https://doi.org/10.1038/s41467-020-19820-8