5U6O

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

Summary for 5U6O

• Entry DOI: 10.2210/pdb5u6o/pdb
• Related: 5U6P
• EMDB information: 8511 8512
• Descriptor: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 (1 entity in total)
• Functional Keywords: pacemaker ion channel, transport protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane ; Multi-pass membrane protein : O60741
• Total number of polymer chains: 4
• Total formula weight: 298574.94

Authors

Lee, C.-H.,MacKinnon, R. (deposition date: 2016-12-08, release date: 2017-01-25, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.5 Å)