• Open Access

Tetrameric structure of SUR2B revealed by electron microscopy of oriented single particles

Authors

  • Constantina Fotinou,

    1. Department of Physiology, Henry Wellcome Centre for Gene Function, University of Oxford, UK
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  • Jussi Aittoniemi,

    1. Department of Physiology, Henry Wellcome Centre for Gene Function, University of Oxford, UK
    2. Department of Biochemistry, University of Oxford, UK
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  • Heidi de Wet,

    1. Department of Physiology, Henry Wellcome Centre for Gene Function, University of Oxford, UK
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  • Ange Polidori,

    1. Laboratoire de Chimie Bioorganique Etudes Systèmes Moléculaires Vectoriels, Universitéd'Avignon et des Pays du Vaucluse, 8400, Avignon, France
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  • Bernard Pucci,

    1. Laboratoire de Chimie Bioorganique Etudes Systèmes Moléculaires Vectoriels, Universitéd'Avignon et des Pays du Vaucluse, 8400, Avignon, France
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  • Mark S. P. Sansom,

    1. Department of Biochemistry, University of Oxford, UK
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  • Catherine Vénien-Bryan,

    1. Department of Biochemistry, University of Oxford, UK
    2. IMPMC, UMR 7590 CNRS-Universite P. et M. Curie, 4, Place Jussieu, F-75005, Paris, France
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    • These authors contributed equally and are joint corresponding authors.
  • Frances M. Ashcroft

    Corresponding author
    • Department of Physiology, Henry Wellcome Centre for Gene Function, University of Oxford, UK
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    • These authors contributed equally and are joint corresponding authors.

Correspondence

F. Ashcroft, Henry Wellcome Centre for Gene Function, Parks Road, Oxford OX1 3PT, UK

Fax: +44 (0) 1865 285813

Tel: +44 (0) 1865 285810

E-mail: frances.ashcroft@dpag.ox.ac.uk

Abstract

The ATP-sensitive potassium (KATP) channel is a hetero-octameric complex that links cell metabolism to membrane electrical activity in many cells, thereby controlling physiological functions such as insulin release, muscle contraction and neuronal activity. It consists of four pore-forming Kir6.2 and four regulatory sulfonylurea receptor (SUR) subunits. SUR2B serves as the regulatory subunit in smooth muscle and some neurones. An integrative approach, combining electron microscopy and homology modelling, has been used to obtain information on the structure of this large (megadalton) membrane protein complex. Single-particle electron microscopy of purified SUR2B tethered to a lipid monolayer revealed that it assembles as a tetramer of four SUR2B subunits surrounding a central hole. In the absence of an X-ray structure, a homology model for SUR2B based on the X-ray structure of the related ABC transporter Sav1866 was used to fit the experimental images. The model indicates that the central hole can readily accommodate the transmembrane domains of the Kir tetramer, suggests a location for the first transmembrane domains of SUR2B (which are absent in Sav1866) and suggests the relative orientation of the SUR and Kir6.2 subunits.

Structured digital abstract

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