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Salt-bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT
Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
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2008 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 378, no 4, 828-839 p.Article in journal (Refereed) Published
Abstract [en]

Active transport of substrates across cytoplasmic membranes is of great physiological, medical and pharmaceutical importance. The glycerol-3-phosphate (G3P) transporter (GlpT) of the E. coli inner membrane is a secondary active antiporter from the ubiquitous major facilitator superfamily that couples the import of G3P to the efflux of inorganic phosphate (Pi) down its concentration gradient. Integrating information from a novel combination of structural, molecular dynamics simulations and biochemical studies, we identify the residues involved directly in binding of substrate to the inward-facing conformation of GlpT, thus defining the structural basis for the substrate-specificity of this transporter. The substrate binding mechanism involves protonation of a histidine residue at the binding site. Furthermore, our data suggest that the formation and breaking of inter- and intradomain salt bridges control the conformational change of the transporter that accompanies substrate translocation across the membrane. The mechanism we propose may be a paradigm for organophosphate:phosphate antiporters.

Place, publisher, year, edition, pages
2008. Vol. 378, no 4, 828-839 p.
Keyword [en]
antiporter; membrane transport; major facilitator superfamily; molecular dynamics simulations; secondary active transport
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:su:diva-24727DOI: 10.1016/j.jmb.2008.03.029ISI: 000256180100006OAI: diva2:198199
Available from: 2008-02-27 Created: 2008-02-27 Last updated: 2012-06-26Bibliographically approved
In thesis
1. Structural modeling of membrane transporter proteins
Open this publication in new window or tab >>Structural modeling of membrane transporter proteins
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A fundamental process of all living organisms - the transport of molecules across cellular membranes through membrane transport proteins - is investigated.

After a brief review of general properties of biological membranes follows a recollection of the major methods of membrane transport that Nature utilizes (Chapter 1). This is followed by a description of important experimental (Chapter 2) and theoretical methods (Chapter 3) for structural studies of membrane proteins. The findings on membrane protein transport in papers I-IV are then summarized (Chapter 4) and important findings are discussed. The remaining text is a discussion on relevant theoretical and experimental methods.

Place, publisher, year, edition, pages
Stockholm: Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi, 2008. 148 p.
membrane protein structure, membrane protein crystallography, membrane protein structure modelling
National Category
Other Industrial Biotechnology
Research subject
Structural Chemistry
urn:nbn:se:su:diva-7402 (URN)978-91-7155-590-8 (ISBN)
Public defence
2008-03-19, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
Available from: 2008-02-27 Created: 2008-02-27Bibliographically approved

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Laaksonen, AattoHovmöller, Sven
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Department of Physical, Inorganic and Structural Chemistry
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