{"doi":"10.1101/2025.01.10.632485","title":"Cryo-EM captures early intermediate steps in dynein activation by LIS1","abstract":"Cytoplasmic dynein-1 (dynein) is an essential molecular motor in eukaryotic cells. Dynein primarily exists in an autoinhibited “Phi” state and requires conformational changes to assemble with its cofactors and form active transport complexes. LIS1, a key dynein regulator, enhances dynein activation and assembly. Using cryo-EM and a human dynein-LIS1 sample incubated with ATP, we mapped the conformational landscape of dynein activation by LIS1. We discovered a novel early intermediate state that we propose precedes our previously identified dynein-LIS1 “Chi” state. Mutations that disrupt this species, which we termed “Pre-Chi”, led to motility defects in vitro, emphasizing its functional importance. Together, our findings provide new insights into how LIS1 relieves dynein autoinhibition during the activation pathway.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":560342,"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":0.9443,"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":881236,"name":"Eva Karasmanis","orcid":"0000-0002-0139-0210","position":1,"is_corresponding":false},{"id":661788,"name":"Agnieszka A. Kendrick","orcid":"0000-0003-3254-4582","position":2,"is_corresponding":false},{"id":239989,"name":"Samara L. Reck‐Peterson","orcid":"0000-0002-1553-465X","position":3,"is_corresponding":false},{"id":239990,"name":"Andrés E. Leschziner","orcid":"0000-0002-7732-7023","position":4,"is_corresponding":false},{"id":1042599,"name":"Kendrick H V Nguyen","orcid":"0009-0000-1928-6991","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:55:42.883572Z","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":[]}