{"doi":"10.1016/j.celrep.2025.116878","title":"Structures of invertebrate PEZO-1 isoforms with a compact architecture and a dispensable pore-distal N-terminal blade","abstract":"PIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define the structural and functional diversity of Caenorhabditis elegans PEZO-1, a single gene with extensive alternative splicing, by determining cryo-electron microscopy structures of three representative isoforms: G (full length), K (lacking the pore-distal N-terminal blade), and L (missing most of the blade). PEZO-1G displays mechanically evoked currents yet adopts a compact, semi-flattened conformation that significantly differs from the mammalian domes. The blades exhibit a three-step slope architecture stabilized by inter-blade latching among transmembrane helical units, yielding a circular, steering-wheel-like arrangement. A wider cap enables distinct blade-cap contacts that stabilize a \"toggle-down\" conformation. Isoform K also exhibits mechanically evoked currents, indicating that the pore-distal N-terminal blade is dispensable for mechanoactivation. Computational membrane-deformation modeling indicates that the isoforms impose distinct curvatures on the bilayer. Our findings indicate an evolutionarily distinct architecture for PEZO-1.","journal":"Cell Reports","year":2025,"id":587562,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9353,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1503247,"name":"Ángela M. Jaramillo-Granada","orcid":"0000-0001-6122-2350","position":1,"is_corresponding":false},{"id":813520,"name":"Daniel J. Orlin","orcid":"0000-0002-7100-4784","position":2,"is_corresponding":false},{"id":1161376,"name":"Wei-Hsiang Weng","orcid":"0000-0001-8146-930X","position":3,"is_corresponding":false},{"id":1345238,"name":"Haosheng Wen","orcid":"0000-0001-7173-7251","position":4,"is_corresponding":false},{"id":352612,"name":"Marcos Sotomayor","orcid":"0000-0002-3333-1805","position":5,"is_corresponding":false},{"id":240292,"name":"Alexander T. Chesler","orcid":"0000-0002-3131-0728","position":6,"is_corresponding":false},{"id":240494,"name":"Matthew L. Baker","orcid":"0000-0001-9039-8523","position":7,"is_corresponding":false},{"id":298139,"name":"Julio F. Cordero-Morales","orcid":"0000-0002-6505-5403","position":8,"is_corresponding":false},{"id":298140,"name":"Valeria Vásquez","orcid":"0000-0001-8494-1534","position":9,"is_corresponding":false},{"id":428191,"name":"Briar Bell","orcid":"0000-0001-9797-6402","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":"41477764","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":[]}