Fig. 5: Proposed activation mechanism and interactions with different functional states in Kv1 channels.
From: Closed state structure of the pore revealed by uncoupled Shaker K+ channel
The progression to activation is from left to right. In the deepest closed state of the channel, all the VSDs are down, and the SF likely resides in the noncanonical state (1). The closed pore is sealed closed by hydrophobic I470 and V474 (1, 2). Upon depolarization, VSDs transit to an active but not-relaxed state (3). The upward movement of the VSDs creates a pull on the S4-S5 linker, yet since not all VSDs are up, the energetic input is not enough to open the pore (4). In the last closed state before opening, or the pre-open state, all four VSDs move up (5), creating enough pull on the S4-S5 linkers (6). In the case of I384R, the channel is most likely stabilized in this pre-open state with newly introduced salt bridges. From the pre-open state, the last concerted movement happens, and the S6 helices undergo a roll and turn movement, opening up the permeation path and expanding the channel laterally (8). At the same time as the pore opens, the lateral movement of the S4-S5 linker drives the VSDs into a different state, the relaxed state (7).
