{"doi":"10.7554/elife.86776","title":"Autoinhibited kinesin-1 adopts a hierarchical folding pattern","abstract":"Conventional kinesin-1 is the primary anterograde motor in cells for transporting cellular cargo. While there is a consensus that the C-terminal tail of kinesin-1 inhibits motility, the molecular architecture of a full-length autoinhibited kinesin-1 remains unknown. Here, we combine crosslinking mass spectrometry (XL-MS), electron microscopy (EM), and AlphaFold structure prediction to determine the architecture of the full-length autoinhibited kinesin-1 homodimer (kinesin-1 heavy chain [KHC]) and kinesin-1 heterotetramer (KHC bound to kinesin light chain 1 [KLC1]). Our integrative analysis shows that kinesin-1 forms a compact, bent conformation through a break in coiled-coil 3. Moreover, our XL-MS analysis demonstrates that kinesin light chains stabilize the folded inhibited state rather than inducing a new structural state. Using our structural model, we show that disruption of multiple interactions between the motor, stalk, and tail domains is required to activate the full-length kinesin-1. Our work offers a conceptual framework for understanding how cargo adaptors and microtubule-associated proteins relieve autoinhibition to promote activation.","journal":"eLife","year":2023,"id":320042,"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":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"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":298272,"name":"Yang Yue","orcid":"0000-0001-7658-2463","position":1,"is_corresponding":false},{"id":51779,"name":"Felipe da Veiga Leprevost","orcid":"0000-0002-8228-5374","position":2,"is_corresponding":false},{"id":230153,"name":"Sarah E. Haynes","orcid":"0000-0003-3225-1691","position":3,"is_corresponding":false},{"id":253569,"name":"Venkatesha Basrur","orcid":"0000-0002-0853-9655","position":4,"is_corresponding":false},{"id":51780,"name":"Alexey I. Nesvizhskii","orcid":"0000-0002-2806-7819","position":5,"is_corresponding":false},{"id":281104,"name":"Kristen J. Verhey","orcid":"0000-0001-9329-4981","position":6,"is_corresponding":false},{"id":297932,"name":"Michael A. Cianfrocco","orcid":"0000-0002-2067-4999","position":7,"is_corresponding":false},{"id":297931,"name":"Zhenyu Tan","orcid":"0000-0001-6491-5806","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T01:07:17.361058Z","pmid":"37910016","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":[]}