{"doi":"10.1101/2020.04.15.043067","title":"Breakage of the Oligomeric CaMKII Hub by the Regulatory Segment of the Kinase","abstract":"Abstract Ca 2+ /calmodulin dependent protein kinase II (CaMKII) is a dodecameric or tetradecameric enzyme with crucial roles in neuronal signaling and cardiac function. Activation of CaMKII is reported to trigger the exchange of subunits between holoenzymes, which can increase spread of the active state. Using mass spectrometry, we now show that peptides derived from the sequence of the CaMKII-α regulatory segment can bind to the CaMKII-α hub assembly and break it into smaller oligomers. Molecular dynamics simulations show that the regulatory segments can dock spontaneously at the interface between hub subunits, trapping large fluctuations in hub structure. Single-molecule fluorescence intensity analysis of human CaMKII-α isolated from mammalian cells shows that activation of CaMKII-α results in the destabilization of the holoenzyme. Our results show how the release of the regulatory segment by activation and phosphorylation could allow it to destabilize the hub, producing smaller CaMKII assemblies that can reassemble to form new holoenzymes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122707,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":564468,"name":"Moitrayee Bhattacharyya","orcid":"0000-0002-2168-1541","position":1,"is_corresponding":false},{"id":565305,"name":"Beryl Xia","orcid":null,"position":2,"is_corresponding":false},{"id":565306,"name":"Young Kwang Lee","orcid":null,"position":3,"is_corresponding":false},{"id":325092,"name":"Serena Muratcioğlu","orcid":"0000-0002-5983-294X","position":4,"is_corresponding":false},{"id":344119,"name":"Darren B. McAffee","orcid":"0000-0002-2565-4938","position":5,"is_corresponding":false},{"id":564469,"name":"Ethan D. McSpadden","orcid":"0000-0002-8705-9341","position":6,"is_corresponding":false},{"id":564470,"name":"Baiyu Qiu","orcid":"0009-0009-6653-6733","position":7,"is_corresponding":false},{"id":302378,"name":"Jay T. Groves","orcid":"0000-0002-3037-5220","position":8,"is_corresponding":false},{"id":522244,"name":"Evan R. Williams","orcid":"0000-0002-1733-3018","position":9,"is_corresponding":false},{"id":344888,"name":"John Kuriyan","orcid":"0000-0002-4414-5477","position":10,"is_corresponding":false},{"id":564467,"name":"Deepti Karandur","orcid":"0000-0002-6949-6337","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:14:55.385653Z","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":[]}