{"doi":"10.1101/2022.02.28.480783","title":"Kinesin-8-specific loop-2 controls the dual activities of the motor domain according to tubulin protofilament shape","abstract":"Kinesin-8s are dual-activity motor proteins that can move processively on microtubules and depolymerize microtubule plus-ends, but their mechanism of combining these distinct activities remains unclear. We addressed this by obtaining cryo-EM structures (2.6-3.9 Å) of Candida albicans Kip3 in different catalytic states on the microtubule lattice and on a curved microtubule end mimic, as well as a microtubule-unbound Ca Kip3-ADP crystal structure (2.0 Å). Together with biochemical analyses of Ca Kip3 and kinesin-1 mutants, we define a model that explains the kinesin-8 mechanism. The microtubule depolymerization activity originates in conformational changes of the kinesin-8 motor core that are amplified by its dynamic loop-2. On curved microtubule ends, loop-1 assists depolymerization by inserting into preceding motor domains, forming head-to-tail arrays of kinesin-8s that complement loop-2 contacts with curved tubulin. On straight tubulin protofilaments in the microtubule lattice, extended loop-2-tubulin contacts inhibit conformational changes in the motor core, but in the ADP-Pi state these contacts are relaxed, allowing neck-linker docking for motility. These tubulin shape-induced alternations between pro-microtubule-depolymerization and pro-motility kinesin states, regulated by loop-2, are the key to the dual activity of kinesin-8 motors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302784,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":570328,"name":"Matthieu P. M. H. Benoit","orcid":"0000-0002-2880-7717","position":1,"is_corresponding":false},{"id":570329,"name":"Ana B. Asenjo","orcid":"0000-0003-3752-9453","position":2,"is_corresponding":false},{"id":891404,"name":"Caitlin Doubleday","orcid":"0000-0002-3337-8881","position":3,"is_corresponding":false},{"id":994948,"name":"Daria N. Trofimova","orcid":"0000-0002-5451-0765","position":4,"is_corresponding":false},{"id":570331,"name":"Hernando Sosa","orcid":"0000-0002-0483-5369","position":5,"is_corresponding":false},{"id":891405,"name":"John S. Allingham","orcid":"0000-0002-0918-3152","position":6,"is_corresponding":false},{"id":891403,"name":"Byron Hunter","orcid":"0000-0002-3331-1708","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T00:32:20.348385Z","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":[]}