{"doi":"10.1101/2022.04.08.487665","title":"Structure of Importin-4 bound to the H3-H4·ASF1 histone·histone chaperone complex","abstract":"Abstract Importin-4 is the primary nuclear import receptor of core histones H3 and H4. Importin-4 binds the H3-H4 dimer and histone-chaperone ASF1 prior to nuclear import, but available structures of Importin-4·histone tail complexes do not explain how Importin-4 recognizes the biologically relevant heterotrimeric H3-H4·ASF1 cargo. Our 3.5 Å Importin-4·H3-H4·ASF1 cryo-electron microscopy structure revealed interactions with H3-H4·ASF1 different those suggested by previous Importin-H3 tail peptide structures. The N-terminal half of Importin-4 clamps the globular histone domain and the H3 αN helix while its C-terminal half binds the H3 N-terminal tail weakly, with negligible tail contribution to binding energy; ASF1 binds H3-H4 without contacting Importin-4. Together, ASF1 and Importin-4 shield nucleosomal interfaces of H3-H4 to chaperone and import it into the nucleus, where Importin-4 undergoes large conformational changes as RanGTP binds to release H3-H4·ASF1. This work explains the mechanisms of nuclear import of full-length H3-H4.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299152,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"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":841402,"name":"Ho Yee Joyce Fung","orcid":"0000-0002-0502-1957","position":1,"is_corresponding":false},{"id":312285,"name":"Yang Li","orcid":"0000-0001-8186-2435","position":2,"is_corresponding":false},{"id":383983,"name":"Zhe Chen","orcid":"0000-0002-1668-4051","position":3,"is_corresponding":false},{"id":345462,"name":"Yuh Min Chook","orcid":"0000-0002-4974-0726","position":4,"is_corresponding":false},{"id":467121,"name":"Natália E. Bernardes","orcid":"0000-0002-6498-0429","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T00:31:40.528568Z","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":[]}