{"doi":"10.1016/j.cell.2016.12.023","title":"Structures of the Human HCN1 Hyperpolarization-Activated Channel","abstract":null,"journal":"Cell","year":2017,"id":686094,"datarank":0.9071058268569417,"base_score":6.0473721790462776,"endowment":6.0473721790462776,"self_citation_contribution":0.9071058268569417,"citation_network_contribution":0.0,"self_endowment_contribution":0.9071058268569417,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":422,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":8,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51699,"name":"Roderick MacKinnon","orcid":"0000-0001-7605-4679","position":1,"is_corresponding":false},{"id":1792496,"name":"Chia-Hsueh Lee","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structures of the Human HCN1 Hyperpolarization-Activated Channel","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<sup>+</sup> channel selectivity filter-forming sequence from which the amino acids create a unique structure that explains Na<sup>+</sup> and K<sup>+</sup> 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.","is_dataset_classified":null,"base_score":6.0473721790462776,"endowment":6.0473721790462776,"datacite_reuse_total":8,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28086084","pmcid":"PMC5496774","openalex_id":"https://openalex.org/W2576780822","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM043949","title":null}],"total_grants":1,"fwci":15.9074,"citation_percentile":0.99484728,"influential_citations":0,"citation_trend":[{"year":2017,"count":18},{"year":2018,"count":56},{"year":2019,"count":39},{"year":2020,"count":43},{"year":2021,"count":51},{"year":2022,"count":32},{"year":2023,"count":55},{"year":2024,"count":59},{"year":2025,"count":47},{"year":2026,"count":22}],"oa_status":"closed","license":"https://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0092867416317391?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867416317391?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.cell.2016.12.023","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28086084","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5496774","host_type":"repository"}],"fields_of_study":["Ion channel regulation and function","Cardiac electrophysiology and arrhythmias","Neuroscience and Neuropharmacology Research","Amino Acid Sequence","Cryoelectron Microscopy","Cyclic AMP","Humans","Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels","Models, Molecular","Potassium Channels","Sequence Alignment"],"mesh_terms":["Cyclic AMP","Amino Acid Sequence","Humans","Models, Molecular","Potassium Channels","Sequence Alignment","Cryoelectron Microscopy","Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels"],"keywords":["HCN channel","Hyperpolarization (physics)","Biophysics","Biology","Ion channel","Gating","Cytoplasm","Potassium channel","Helix (gastropod)","Intracellular","Membrane potential","Cell biology","Biochemistry","Chemistry","Stereochemistry","Cryo-electron microscopy","Atomic Structure","Voltage-dependent Gating","Ion Selectivity","Rhythmic Firing","Cardiac And Neuronal Pacemaker","Hyperpolarization-activated Ion 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