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In Vivo Trp Scanning of the Small Multidrug Resistance Protein EmrE Confirms 3D Structure Models
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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2013 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 425, no 22, 4642-4651 p.Article in journal (Refereed) Published
Abstract [en]

The quaternary structure of the homodimeric small multidrug resistance protein EmrE has been studied intensely over the past decade. Structural models derived from both two- and three-dimensional crystals show EmrE as an anti-parallel homodimer. However, the resolution of the structures is rather low and their relevance for the in vivo situation has been questioned. Here, we have challenged the available structural models by a comprehensive in vivo Trp scanning of all four transmembrane helices in EmrE. The results are in close agreement with the degree of lipid exposure of individual residues predicted from coarse-grained molecular dynamics simulations of the anti-parallel dimeric structure obtained by X-ray crystallography, strongly suggesting that the X-ray structure provides a good representation of the active in vivo form of EmrE.

Place, publisher, year, edition, pages
2013. Vol. 425, no 22, 4642-4651 p.
Keyword [en]
EmrE, multidrug resistance, Trp scan
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-94831DOI: 10.1016/j.jmb.2013.07.039ISI: 000328100500048OAI: oai:DiVA.org:su-94831DiVA: diva2:658716
Available from: 2013-10-22 Created: 2013-10-15 Last updated: 2017-12-06Bibliographically approved
In thesis
1. EmrE, a puzzling transporter: Assembly, biogenesis and evolution of a dual-topology membrane protein
Open this publication in new window or tab >>EmrE, a puzzling transporter: Assembly, biogenesis and evolution of a dual-topology membrane protein
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological membranes are the key to cell existence, as they are able to both isolate and connect their interior with the environment. Membranes are composed of lipids and proteins that create a semi-permeable barrier; because the lipid bilayer stops free diffusion of most molecules and ions, membrane proteins play an important role in connecting the interior of the cell with its environment. They function as receptors, sensing signals to trigger a response; cell adhesion molecules, holding neighboring cells together, or transporters and channels importing nutrients and extruding waste, among other chemical compounds, in a controlled manner.

In order for membrane proteins to function correctly, proper insertion, folding and oligomerization in the bilayer is essential. While most membrane proteins adopt a unique orientation in the membrane, some proteins adopt multiple topologies. A well-known case is the dual-topology membrane proteins that adopt two opposite orientations in the membrane. The best-studied dual-topology protein is EmrE, a dimeric multidrug transporter found in Escherichia coli, and other bacteria.

The existence of dual-topology proteins raises many questions regarding oligomerization, biogenesis and evolution of membrane proteins. In this thesis, EmrE has been used as a model protein to study some of these issues. Our goals were (i) to settle the controversy regarding whether the arrangement of the monomers within the EmrE dimer is parallel or antiparallel, (ii) to test the validity of the published X-ray structure by in vivo experiments and, (iii) to elucidate the mechanism of membrane insertion (iv) and the evolution of dual-topology membrane proteins.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2013. 68 p.
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-94830 (URN)978-91-7447-797-9 (ISBN)
Public defence
2013-12-06, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
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Note

At the time of the doctoral defence the following papers were unpublished and had a status as follows: Paper 2: Epub ahead of print; Paper 4: Manuscript

Available from: 2013-11-14 Created: 2013-10-15 Last updated: 2013-11-05Bibliographically approved

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