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Mutation-Induced Po...
Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression
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- Anandapadmanaban, Madhanagopal (author)
- Linköpings universitet,Institutionen för fysik, kemi och biologi,Tekniska fakulteten
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- Pilstål, Robert (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Andrésen, Cecilia (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Trewhella, Jill (author)
- Linköpings universitet,Kemi,Tekniska fakulteten,University of Sydney, Australia
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- Moche, Martin (author)
- Karolinska Institutet
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- Wallner, Björn (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Sunnerhagen, Maria (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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(creator_code:org_t)
- CELL PRESS, 2016
- 2016
- English.
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In: Structure. - : CELL PRESS. - 0969-2126 .- 1878-4186. ; 24:8, s. 1311-1321
- Related links:
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
Close
- MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 angstrom) presented here is closely similar to wildtype MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members.
Subject headings
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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