{"doi":"10.1016/j.jmb.2025.169125","title":"The Structure of the Drp1 Lattice on Membrane","abstract":"• The structure of the mitochondrial fission protein Drp1 has been determined by cryo-EM. • Structure determination of the heterogeneous tubular structure was facilitated using the RASTR algorithm. • Drp1 on membrane forms an asymmetric tetramer with the GTPase domains in two different states. • Different Drp1 GTPase domain conformations give rise to a model for membrane constriction. Mitochondrial health relies on the membrane fission mediated by dynamin-related protein 1 (Drp1). Previous structural studies of Drp1 on remodeled membranes were hampered by heterogeneity, leaving a critical gap in the understanding of the mitochondrial fission mechanisms. Here we present a cryo-electron microscopy structure of full-length human Drp1 decorated on membrane tubules. Using the reconstruction of average subtracted tubular regions (RASTR) technique, we report that Drp1 forms a locally ordered lattice along the tubule without global helical symmetry. The filaments in the lattice are similar to dynamin rungs with conserved stalk interactions. Adjacent filaments are connected by GTPase domain interactions in a novel stacked conformation. We identified two states of the Drp1 lattice among the heterogenous dataset representing conformational changes around hinge 1. Additionally, we observed contact between Drp1 and membrane that can be assigned to the variable domain sequence. Together these structures revealed a putative mechanism by which Drp1 constricts mitochondria membranes in a stepwise, “ratchet” manner.","journal":"Journal of Molecular Biology","year":2025,"id":517248,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.944,"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":788656,"name":"Kristy Rochon","orcid":"0000-0001-5692-6046","position":1,"is_corresponding":false},{"id":910603,"name":"Anelise N Hutson","orcid":null,"position":2,"is_corresponding":false},{"id":308881,"name":"Scott M. Stagg","orcid":"0000-0001-8855-4152","position":3,"is_corresponding":false},{"id":329334,"name":"Jason A. Mears","orcid":"0000-0002-5199-4872","position":4,"is_corresponding":false},{"id":1257158,"name":"Ruizhi Peng","orcid":"0000-0001-6057-8961","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:59.410472Z","pmid":"40185198","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":[]}