Premium
Tetrameric structure of SUR2B revealed by electron microscopy of oriented single particles
Author(s) -
Fotinou Constantina,
Aittoniemi Jussi,
Wet Heidi,
Polidori Ange,
Pucci Bernard,
Sansom Mark S. P.,
VénienBryan Catherine,
Ashcroft Frances M.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12097
Subject(s) - tetramer , electron microscope , chemistry , biophysics , protein subunit , homology modeling , transmembrane protein , transmembrane domain , cryo electron microscopy , crystallography , membrane , membrane protein , biochemistry , receptor , biology , physics , gene , optics , enzyme
The ATP ‐sensitive potassium ( K ATP ) 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 abstractSUR2B and SUR2B bind by electron microscopy ( View interaction ) SUR2B and SUR2B bind by molecular sieving ( View interaction )