Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs

• DOI: 10.7554/elife.37558
• Publication Date: 2018-08-15T12:00:22Z
• Authors: Doreen Matthies; Chanhyung Bae; Gilman ES Toombes; Tara Fox; Alberto Bartesaghi; Sriram Subramaniam; Kenton Jon Swartz
• Keywords: QH301-705.5; Protein Conformation; Science; Lipid Bilayers; Kv channel; Crystallography, X-Ray; Nanocomposites; 03 medical and health sciences; Shab Potassium Channels; Kv1.2 Potassium Channel; structural biology; Animals; Biology (General); C-type inactivation; 0303 health sciences; electron microscopy; lipid nanodisc; Q; Cryoelectron Microscopy; R; cryo-EM structure; Rats; Potassium; Medicine; Ion Channel Gating; Neuroscience

Voltage-activated potassium (Kv) channels open to conduct K+ ions in response to membrane depolarization, and subsequently enter non-conducting states through distinct mechanisms of inactivation. X-ray structures of detergent-solubilized Kv channels appear to have captured an open state even though a non-conducting C-type inactivated state would predominate in membranes in the absence of a transmembrane voltage. However, structures for a voltage-activated ion channel in a lipid bilayer environment have not yet been reported. Here we report the structure of the Kv1.2–2.1 paddle chimera channel reconstituted into lipid nanodiscs using single-particle cryo-electron microscopy. At a resolution of ~3 Å for the cytosolic domain and ~4 Å for the transmembrane domain, the structure determined in nanodiscs is similar to the previously determined X-ray structure. Our findings show that large differences in structure between detergent and lipid bilayer environments are unlikely, and enable us to propose possible structural mechanisms for C-type inactivation.