Fig. 5: Key states in the process of BK channel inactivation by the β2 subunit.

a In the absence of Ca²⁺, the β2 chain binds to the resting gating ring and the channel is closed. Upon Ca²⁺-binding to the gating ring, both an intermediate (b) and an open (c) state form. b In the intermediate state, the gating ring (Ca²⁺ is bound to both RCK sites although the gating ring is still in the resting conformation) is slightly rotated with respect to the transmembrane domain, the S6 helix becomes partially unwound around the glycine hinge and slightly more dilated than in the closed state, and the β2 chain binds at a different location on the gating ring. c In the open state, the gating ring is activated and the S6 helices bend at the hinge glycine to open the pore wider. We did not observe an open, not inactivated state in our study. d When the pore is open, the β2 ball enters the pore to inactivate the channel and may also bind at an alternate site that does not (completely) occlude the pore. This state is drawn slightly transparent to convey its uncertainty. e The β2 ball binds to the pore and plugs the permeation pathway to inactivate the channel. The model shown highlights the main conformational states structurally identified here and it is not meant to account for all previously reported functional data.