{"doi":"10.1101/2022.05.27.493711","title":"Structural dynamics underlying gating and regulation in IP <sub>3</sub> R channel","abstract":"ABSTRACT Inositol-1,4,5-trisphosphate receptors (IP 3 Rs) are activated by IP 3 and Ca 2+ and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IP 3 R1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP 3 , Ca 2+ and ATP in IP 3 R1, revealing conformational changes that couple ligand-binding to channel opening. Using a GMM based deep learning approach and 3D variability analysis, we extracted dynamic properties of the key protein domains. From this, we find that IP 3 binding relies upon intrinsic flexibility of the cytoplasmic ARM2 domain. Our results highlight a key role of dynamic side chains surrounding the ion conduction path in regulating gating behavior of IP 3 R channels. Altogether, this work defines a structural platform for mechanistic understanding of the molecular dynamics underlying ligand-binding, activation and regulation of the IP 3 R activity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303555,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9388,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":630105,"name":"Mariah R. Baker","orcid":"0000-0002-1613-9387","position":1,"is_corresponding":false},{"id":753917,"name":"Lara E. Terry","orcid":"0000-0002-0200-4334","position":2,"is_corresponding":false},{"id":542325,"name":"Vikas Arige","orcid":"0000-0002-0589-1880","position":3,"is_corresponding":false},{"id":561591,"name":"Muyuan Chen","orcid":"0000-0003-1311-7868","position":4,"is_corresponding":false},{"id":630106,"name":"Alexander Seryshev","orcid":"0000-0001-5643-0251","position":5,"is_corresponding":false},{"id":240494,"name":"Matthew L. Baker","orcid":"0000-0001-9039-8523","position":6,"is_corresponding":false},{"id":233008,"name":"Steven J. Ludtke","orcid":"0000-0002-1903-1574","position":7,"is_corresponding":false},{"id":147718,"name":"David I Yule","orcid":"0000-0002-6743-0668","position":8,"is_corresponding":false},{"id":561595,"name":"Irina I. Serysheva","orcid":"0000-0001-6266-3422","position":9,"is_corresponding":false},{"id":561594,"name":"Guizhen Fan","orcid":"0000-0002-6741-6989","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"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":[]}