7NP4

cAMP-bound rabbit HCN4 stabilized in LMNG-CHS detergent mixture

7NP4 の概要

• エントリーDOI: 10.2210/pdb7np4/pdb
• EMDBエントリー: 12513
• 分子名称: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4,Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE (2 entities in total)
• 機能のキーワード: hcn channels, camp, ion transport, membrane protein
• 由来する生物種: Oryctolagus cuniculus (Rabbit); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 395407.73

構造登録者

Giese, H.,Chaves-Sanjuan, A.,Saponaro, A.,Clarke, O.,Bolognesi, M.,Mancia, F.,Hendrickson, W.A.,Thiel, G.,Santoro, B.,Moroni, A. (登録日: 2021-02-26, 公開日: 2021-08-11, 最終更新日: 2025-07-09)

主引用文献

Saponaro, A.,Bauer, D.,Giese, M.H.,Swuec, P.,Porro, A.,Gasparri, F.,Sharifzadeh, A.S.,Chaves-Sanjuan, A.,Alberio, L.,Parisi, G.,Cerutti, G.,Clarke, O.B.,Hamacher, K.,Colecraft, H.M.,Mancia, F.,Hendrickson, W.A.,Siegelbaum, S.A.,DiFrancesco, D.,Bolognesi, M.,Thiel, G.,Santoro, B.,Moroni, A.
Gating movements and ion permeation in HCN4 pacemaker channels.
Mol.Cell, 81:2929-2943.e6, 2021

PubMed Abstract: The HCN1-4 channel family is responsible for the hyperpolarization-activated cation current I/I that controls automaticity in cardiac and neuronal pacemaker cells. We present cryoelectron microscopy (cryo-EM) structures of HCN4 in the presence or absence of bound cAMP, displaying the pore domain in closed and open conformations. Analysis of cAMP-bound and -unbound structures sheds light on how ligand-induced transitions in the channel cytosolic portion mediate the effect of cAMP on channel gating and highlights the regulatory role of a Mg coordination site formed between the C-linker and the S4-S5 linker. Comparison of open/closed pore states shows that the cytosolic gate opens through concerted movements of the S5 and S6 transmembrane helices. Furthermore, in combination with molecular dynamics analyses, the open pore structures provide insights into the mechanisms of K/Na permeation. Our results contribute mechanistic understanding on HCN channel gating, cyclic nucleotide-dependent modulation, and ion permeation.

PubMed: 34166608
DOI: 10.1016/j.molcel.2021.05.033

実験手法

ELECTRON MICROSCOPY (3.3 Å)