{"doi":"10.1038/s42003-021-02729-3","title":"PIP2-dependent coupling of voltage sensor and pore domains in Kv7.2 channel","abstract":"Abstract Phosphatidylinositol-4,5-bisphosphate (PIP 2 ) is a signaling lipid which regulates voltage-gated K v 7/ KCNQ potassium channels. Altered PIP 2 sensitivity of neuronal K v 7.2 channel is involved in KCNQ2 epileptic encephalopathy. However, the molecular action of PIP 2 on K v 7.2 gating remains largely elusive. Here, we use molecular dynamics simulations and electrophysiology to characterize PIP 2 binding sites in a human K v 7.2 channel. In the closed state, PIP 2 localizes to the periphery of the voltage-sensing domain (VSD). In the open state, PIP 2 binds to 4 distinct interfaces formed by the cytoplasmic ends of the VSD, the gate, intracellular helices A and B and their linkers. PIP 2 binding induces bilayer-interacting conformation of helices A and B and the correlated motion of the VSD and the pore domain, whereas charge-neutralizing mutations block this coupling and reduce PIP 2 sensitivity of K v 7.2 channels by disrupting PIP 2 binding. These findings reveal the allosteric role of PIP 2 in K v 7.2 channel activation.","journal":"Communications Biology","year":2021,"id":171995,"datarank":0.8892722403799633,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.3948967104793139,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.3948967104793139,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":25,"citers_with_citation_signal":19,"citers_with_endowment":19,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":true,"deposit_databanks":{"figshare":["10.6084/m9.figshare.15181038"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":333542,"name":"Jiaren Zhang","orcid":"0000-0002-7627-0950","position":1,"is_corresponding":false},{"id":343871,"name":"Eung Chang Kim","orcid":"0000-0002-8000-6271","position":2,"is_corresponding":false},{"id":146339,"name":"Kin Lam","orcid":null,"position":3,"is_corresponding":false},{"id":343876,"name":"Hee Jung Chung","orcid":"0000-0002-5555-9907","position":4,"is_corresponding":false},{"id":98027,"name":"Emad Tajkhorshid","orcid":"0000-0001-8434-1010","position":5,"is_corresponding":false},{"id":295273,"name":"Shashank Pant","orcid":"0000-0002-8222-3616","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-18T23:46:37.150824Z","pmid":"34650221","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}