Cryo-EM Structure of the BK Ion Channel in a Lipid Membrane

Abstract

The large-conductance voltage- and Ca2+-activated potassium (BK) channel has many physiological roles including the control of firing patterns in neurons, the modulation of the tone of blood vessels and the regulation of heart rate. Among ion channels, it has served as a model system because of its remarkable ion-permeation properties and its accessibility for studies of allosteric control of gating.As shown in both structural and functional studies, the lipid membrane environment has played an essential role for membrane proteins. To restore the lipid membrane environment, BK channels were reconstituted into liposomes (lipid vesicles) for both functional and structural studies. In 2009, we have reported the full-length BK structure in lipid environment at a resolution of 1.7nm using “random spherically constrained” (RSC) single-particle Cryo-EM method. Recent breakthrough in hardware and the optimization of image collection and processing techniques make it possible to achieve a higher resolution. Here, we present the BK structure in a lipid membrane in the closed state with a greatly improved resolution. The helices in the transmembrane region can be clearly identified, and the helix S0 is identified to be next to helices S2 and S3.