{"doi":"10.1002/pro.4787","title":"The variable domain from dynamin‐related protein 1 promotes liquid–liquid phase separation that enhances its interaction with cardiolipin‐containing membranes","abstract":"Dynamins are an essential superfamily of mechanoenzymes that remodel membranes and often contain a \"variable domain\" important for regulation. For the mitochondrial fission dynamin, dynamin-related protein 1, a regulatory role for the variable domain (VD) is demonstrated by gain- and loss-of-function mutations, yet the basis for this is unclear. Here, the isolated VD is shown to be intrinsically disordered and undergo a cooperative transition in the stabilizing osmolyte trimethylamine N-oxide. However, the osmolyte-induced state is not folded and surprisingly appears as a condensed state. Other co-solutes including known molecular crowder Ficoll PM 70, also induce a condensed state. Fluorescence recovery after photobleaching experiments reveal this state to be liquid-like indicating the VD undergoes a liquid-liquid phase separation under crowding conditions. These crowding conditions also enhance binding to cardiolipin, a mitochondrial lipid, which appears to promote phase separation. Since dynamin-related protein 1 is found assembled into discrete punctate structures on the mitochondrial surface, the inference from the present work is that these structures might arise from a condensed state involving the VD that may enable rapid tuning of mechanoenzyme assembly necessary for fission.","journal":"Protein Science","year":2023,"id":371674,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1095180,"name":"Kyle A. Ross","orcid":"0000-0002-0471-169X","position":1,"is_corresponding":false},{"id":1131681,"name":"Mehran Bagheri","orcid":"0000-0001-9976-805X","position":2,"is_corresponding":false},{"id":1132190,"name":"Elizabeth N. Lanum","orcid":null,"position":3,"is_corresponding":false},{"id":1132191,"name":"M. Adil Khan","orcid":null,"position":4,"is_corresponding":false},{"id":1076544,"name":"Christine E. Jennings","orcid":null,"position":5,"is_corresponding":false},{"id":632399,"name":"Megan Cleland Harwig","orcid":"0000-0003-2140-5739","position":6,"is_corresponding":false},{"id":354439,"name":"Nolan W. Kennedy","orcid":"0000-0002-2944-5439","position":7,"is_corresponding":false},{"id":413796,"name":"Vincent J. Hilser","orcid":"0000-0002-7173-0073","position":8,"is_corresponding":false},{"id":1131682,"name":"James L. Harden","orcid":"0000-0002-4118-7209","position":9,"is_corresponding":false},{"id":632401,"name":"R. Blake Hill","orcid":"0000-0001-6228-3905","position":10,"is_corresponding":false},{"id":239689,"name":"Ammon E. Posey","orcid":"0000-0002-1445-6522","position":0,"is_corresponding":true}],"reference_count":108,"raw_metadata":null,"created_at":"2026-07-19T01:15:49.453761Z","pmid":"37743569","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":[]}