Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain was written by Chi, Gamma;Liang, Qiansheng;Sridhar, Akshay;Cowgill, John B.;Sader, Kasim;Radjainia, Mazdak;Qian, Pu;Castro-Hartmann, Pablo;Venkaya, Shayla;Singh, Nanki Kaur;McKinley, Gavin;Fernandez-Cid, Alejandra;Mukhopadhyay, Shubhashish M. M.;Burgess-Brown, Nicola A.;Delemotte, Lucie;Covarrubias, Manuel;Durr, Katharina L.. And the article was included in Nature Communications in 2022.HPLC of Formula: 11024-24-1 This article mentions the following:
Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Addnl. interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by mol. dynamics simulations, electrophysiol. and mutational analyses, we identify several residues in the S4/S5 linker which influence the gating kinetics and an electrostatic interaction between acidic residues in α6 of T1 and R449 in the pore-flanking S6T helixes. These findings provide insights into gating control and disease mechanisms and may guide strategies for the design of pharmaceutical drugs targeting Kv3 channels. In the experiment, the researchers used many compounds, for example, Digitonin (cas: 11024-24-1HPLC of Formula: 11024-24-1).
Digitonin (cas: 11024-24-1) belongs to tetrahydropyran derivatives. In organic synthesis, the 2-tetrahydropyranyl group is used as a protecting group for alcohols. One classic procedure for the organic synthesis of tetrahydropyran is by hydrogenation of the 3,4-isomer of dihydropyran with Raney nickel.HPLC of Formula: 11024-24-1
Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics