5U6O

Structure of the human HCN1 hyperpolarization-activated cyclic nucleotide-gated ion channel

5U6O の概要

• エントリーDOI: 10.2210/pdb5u6o/pdb
• 関連するPDBエントリー: 5U6P
• EMDBエントリー: 8511 8512
• 分子名称: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 (1 entity in total)
• 機能のキーワード: pacemaker ion channel, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : O60741
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 298574.94

構造登録者

Lee, C.-H.,MacKinnon, R. (登録日: 2016-12-08, 公開日: 2017-01-25, 最終更新日: 2024-03-13)

主引用文献

Lee, C.H.,MacKinnon, R.
Structures of the Human HCN1 Hyperpolarization-Activated Channel.
Cell, 168:111-120.e11, 2017

PubMed Abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the control of rhythmic activity in cardiac and neuronal pacemaker cells. In HCN, the polarity of voltage dependence is uniquely reversed. Intracellular cyclic adenosine monophosphate (cAMP) levels tune the voltage response, enabling sympathetic nerve stimulation to increase the heart rate. We present cryo-electron microscopy structures of the human HCN channel in the absence and presence of cAMP at 3.5 Å resolution. HCN channels contain a K channel selectivity filter-forming sequence from which the amino acids create a unique structure that explains Na and K permeability. The voltage sensor adopts a depolarized conformation, and the pore is closed. An S4 helix of unprecedented length extends into the cytoplasm, contacts the C-linker, and twists the inner helical gate shut. cAMP binding rotates cytoplasmic domains to favor opening of the inner helical gate. These structures advance understanding of ion selectivity, reversed polarity gating, and cAMP regulation in HCN channels.

PubMed: 28086084
DOI: 10.1016/j.cell.2016.12.023

実験手法

ELECTRON MICROSCOPY (3.5 Å)