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Why Have Small Multidrug Resistance Proteins Not Evolved into Fused, Internally Duplicated Structures?
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2014 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 426, no 11, 2246-2254 p.Article in journal (Refereed) Published
Abstract [en]

The increasing number of solved membrane protein structures has led to the recognition of a common feature in a large fraction of the small-molecule transporters: inverted repeat structures, formed by two fused homologous membrane domains with opposite orientation in the membrane. An evolutionary pathway in which the ancestral state is a single gene encoding a dual-topology membrane protein capable of forming antiparallel homodimers has been posited. A gene duplication event enables the evolution of two oppositely orientated proteins that form antiparallel heterodimers. Finally, fusion of the two genes generates an internally duplicated transporter with two oppositely orientated membrane domains. Strikingly, however, in the small multidrug resistance (SMR) family of transporters, no fused, internally duplicated proteins have been found to date. Here, we have analyzed fused versions of the dual-topology transporter EmrE, a member of the SMR family, by blue-native PAGE and in vivo activity measurements. We find that fused constructs give rise to both intramolecular inverted repeat structures and competing intermolecular dimers of varying activity. The formation of several intramolecularly and intermolecularly paired species indicates that a gene fusion event may lower the overall amount of active protein, possibly explaining the apparent absence of fused SMR proteins in nature.

Place, publisher, year, edition, pages
2014. Vol. 426, no 11, 2246-2254 p.
Keyword [en]
EmrE, dual topology, inverted repeat structure, evolution
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-105912DOI: 10.1016/j.jmh.2014.03.012ISI: 000336699300008OAI: oai:DiVA.org:su-105912DiVA: diva2:733271
Funder
Swedish Cancer SocietySwedish Research CouncilSwedish Foundation for Strategic Research , 232648EU, European Research CouncilKnut and Alice Wallenberg Foundation
Note

AuthorCount:5;

Available from: 2014-07-08 Created: 2014-07-08 Last updated: 2017-12-05Bibliographically approved

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Lloris-Garcera, PilarRapp, Mikaelavon Heijne, Gunnar
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