Structure of the ILT Mutant Shaker K+ Channel and the Mechanism of Voltage Activation
Agrawal, R.; Uriarte, R. M.; Anwandter, B. P.; Thomas, T.; Blachowicz, L.; Koh, Y. H.; Koh, Y.; Bezanila, F.; Perozo, E.; Roux, B.
Show abstract
To understand the process of voltage activation in Kv channels, we determined the cryo-EM structure of the Shaker channel ILT mutant (V369I, I372L, S376T), known to partially decouple the gating charge movement of the voltage sensing domain (VSD) and the opening of the pore domain (PD). The structure captures a previously unobserved intermediate state in which the VSD is only partially activated while the PD remains closed. Combined with computational modeling based on AlphaFold2 predictions and molecular dynamics simulations, it is shown that VSD activation does not mechanically pull the gate open, but instead induces a dynamic shift in the population equilibrium of the VSD-PD linker, providing the basis for electromechanical coupling between the two domains.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na+ channels in nanodisc 97%
- The BK channel-NS1619 agonist complex reveals molecular insights on allosteric activation gating 96%
- Structure of human Nav1.5 reveals the fast inactivation-related segments as a mutational hotspot for the Long QT Syndrome 96%
Similar papers in this journal
Similar papers in this journal
- An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing Asparagine 96%
- Calcium-induced environmental adaptability of the blood protein vitronectin 96%
- Pathways of inter- and intrasubunit allosteric signaling in the C-linker disk and cyclic nucleotide-binding domain of HCN2 channels 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.