{"doi":"10.7554/elife.109308","title":"Accessibility of the unstructured α-tubulin C-terminal tail is controlled by microtubule lattice conformation","abstract":"Microtubules are cytoskeletal filaments that self-assemble from the protein tubulin, a heterodimer of α-tubulin and β-tubulin, and are important for cell mechanics, migration, and division. Much work has focused on how the nucleotide state of β-tubulin regulates the structure and dynamics of microtubules. In contrast, less is known about the structure and function of the C-terminal tails (CTTs) of α- and β-tubulin which are thought to freely protrude from the surface of the microtubule. To study the CTT of α-tubulin, we developed three different biosensors that bind the tyrosinated α-tubulin CTT (Y-αCTT). Surprisingly, live imaging of the probes indicates that the Y-αCTT is minimally accessible along the microtubule lattice under normal cellular conditions. Lattice binding of the Y-αCTT probes can be increased by three different ways of changing the tubulin conformational state: the drug Taxol, expression of microtubule-associated proteins (MAPs) that recognize or promote an expanded tubulin conformation, or expression of tubulin that cannot hydrolyze GTP. Molecular dynamics simulations indicate that the Y-αCTT undergoes numerous transient interactions with the bodies of α-tubulin and β-tubulin in the lattice, and that the frequency of these interactions is regulated by the tubulin nucleotide state. These findings suggest that accessibility of the Y-αCTT is locally governed by nucleotide- and MAP-dependent conformational changes to tubulin subunits within the microtubule lattice.","journal":"eLife","year":2025,"id":559410,"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":0.9491,"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":355732,"name":"Morgan L. Pimm","orcid":"0000-0001-6370-1435","position":1,"is_corresponding":false},{"id":506777,"name":"Ezekiel C. Thomas","orcid":"0000-0002-9810-0477","position":2,"is_corresponding":false},{"id":298272,"name":"Yang Yue","orcid":"0000-0001-7658-2463","position":3,"is_corresponding":false},{"id":1245148,"name":"Patrick DeLear","orcid":"0000-0002-1013-0138","position":4,"is_corresponding":false},{"id":689355,"name":"T. Lynne Blasius","orcid":"0000-0003-3190-4304","position":5,"is_corresponding":false},{"id":297932,"name":"Michael A. Cianfrocco","orcid":"0000-0002-2067-4999","position":6,"is_corresponding":false},{"id":878253,"name":"Morgan E. DeSantis","orcid":"0000-0002-4096-8548","position":7,"is_corresponding":false},{"id":1461239,"name":"Ryota Horiuchi","orcid":null,"position":8,"is_corresponding":false},{"id":891483,"name":"Takumi Higaki","orcid":"0000-0002-1379-3930","position":9,"is_corresponding":false},{"id":281103,"name":"David Sept","orcid":"0000-0003-3719-2483","position":10,"is_corresponding":false},{"id":498078,"name":"Ryoma Ohi","orcid":"0000-0001-9841-134X","position":11,"is_corresponding":false},{"id":281104,"name":"Kristen J. Verhey","orcid":"0000-0001-9329-4981","position":12,"is_corresponding":false},{"id":689354,"name":"Takashi Hotta","orcid":"0000-0002-9497-0950","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41662400","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":[]}