{"doi":"10.7554/elife.66226","title":"Structural basis for allosteric control of the SERCA-Phospholamban membrane complex by Ca2+ and phosphorylation","abstract":"Phospholamban (PLN) is a mini-membrane protein that directly controls the cardiac Ca 2+ -transport response to β-adrenergic stimulation, thus modulating cardiac output during the fight-or-flight response. In the sarcoplasmic reticulum membrane, PLN binds to the sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA), keeping this enzyme's function within a narrow physiological window. PLN phosphorylation by cAMP-dependent protein kinase A or increase in Ca 2+ concentration reverses the inhibitory effects through an unknown mechanism. Using oriented-sample solid-state NMR spectroscopy and replica-averaged NMR-restrained structural refinement, we reveal that phosphorylation of PLN’s cytoplasmic regulatory domain signals the disruption of several inhibitory contacts at the transmembrane binding interface of the SERCA-PLN complex that are propagated to the enzyme’s active site, augmenting Ca 2+ transport. Our findings address long-standing questions about SERCA regulation, epitomizing a signal transduction mechanism operated by posttranslationally modified bitopic membrane proteins.","journal":"eLife","year":2021,"id":158812,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9639,"is_data_producer":false,"deposit_databanks":null,"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":668825,"name":"U. Venkateswara Reddy","orcid":null,"position":1,"is_corresponding":false},{"id":418593,"name":"Songlin Wang","orcid":"0000-0002-7588-7377","position":2,"is_corresponding":false},{"id":668274,"name":"Erik K. Larsen","orcid":"0000-0002-7553-212X","position":3,"is_corresponding":false},{"id":409123,"name":"Tata Gopinath","orcid":"0000-0002-5237-2135","position":4,"is_corresponding":false},{"id":510142,"name":"Martin Gustavsson","orcid":"0000-0002-3015-2043","position":5,"is_corresponding":false},{"id":417548,"name":"Rǎzvan L. Cornea","orcid":"0000-0001-5739-0992","position":6,"is_corresponding":false},{"id":417547,"name":"David D. Thomas","orcid":"0000-0002-8822-2040","position":7,"is_corresponding":false},{"id":615301,"name":"Alfonso De Simone","orcid":"0000-0001-8789-9546","position":8,"is_corresponding":false},{"id":364784,"name":"Gianluigi Veglia","orcid":"0000-0002-2795-6964","position":9,"is_corresponding":false},{"id":409124,"name":"Daniel K. Weber","orcid":"0000-0001-8400-767X","position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":null,"created_at":"2026-07-18T23:44:30.791367Z","pmid":"33978571","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":[]}