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The pharmacological properties of ion channels are inextricably linked to their in situ subunit composition, yet such information is presently not available on a routine basis.
Study objective
Protein Tomography™ was employed to analyze the assembly of the ion channel and to provide information on multimericity and conformation of the macromolecular complex. The analysis was performed for AstraZeneca, Södertälje, Sweden.
Conclusions
Ion-channel expressed on the plasma membrane of RIN cells. The ion channel (white) , four subunits of the tetramer (encircled in red on lower image), central pore opening (grey), and the antibodies (blue) used to locate the ion-channel in the cell, visualized using Tomography of Proteins. The channel is pre-organized into dual dimers that are fused (dashed red line in lower image) and span the channel longitudinally. The lipid bilayer extends over “the neck region” of the protein complex. The cell membrane is not visible due to the staining technique used. However, it is reflected as a negative space in the 3-D reconstruction of cellular material. The ion channel is approximately 9-10 nm in width and 15-17 nm in height.
Ion channel dual dimers, presumably in the process of forming a tetrameric complex (in rat dorsal root ganglia cells). The separate monomeric units (white) constituting the dimers are outlined in red. Only a small component of the primary antibody marking subunit (light blue) is included in the figure. The dimers are bridged by a protein complex (dark grey), possibly chaperone proteins. The dimers are about 15–17 nm in height and 13–14 nm in extracellular width.