{"doi":"10.1073/pnas.0507960102","title":"The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G","abstract":"<jats:p>\n            Eukaryotic translation initiation factor (eIF) 5 is crucial for the assembly of the eukaryotic preinitiation complex. This activity is mediated by the ability of its C-terminal HEAT domain to interact with eIF1, eIF2, and eIF3 in the multifactor complex and with eIF4G in the 48S complex. However, the binding sites for these factors on eIF5–C-terminal domain (CTD) have not been known. Here we present a homology model for eIF5-CTD based on the HEAT domain of eIF2Bε. We show that the binding site for eIF2β is located in a surface area containing aromatic and acidic residues (aromatic/acidic boxes), that the binding sites for eIF1 and eIF3c are located in a conserved surface region of basic residues, and that eIF4G binds eIF5-CTD at an interface overlapping with the acidic area. Mutations in these distinct eIF5 surface areas impair\n            <jats:italic>GCN4</jats:italic>\n            translational control by disrupting preinitiation complex interactions. These results indicate that the eIF5 HEAT domain is a critical nucleation core for preinitiation complex assembly and function.\n          </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2005,"id":21572,"datarank":2.887046415703927,"base_score":4.418840607796598,"endowment":4.418840607796598,"self_citation_contribution":0.6628260911694899,"citation_network_contribution":2.2242203245344374,"self_endowment_contribution":0.6628260911694899,"citer_contribution":2.2242203245344374,"corpus_percentile":null,"corpus_rank":null,"citation_count":82,"citer_count":57,"citers_with_citation_signal":49,"citers_with_endowment":49,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":138387,"name":"Chingakham Ranjit Singh","orcid":null,"position":1,"is_corresponding":false},{"id":138388,"name":"Assen Marintchev","orcid":null,"position":2,"is_corresponding":false},{"id":138389,"name":"Nathan S. Hall","orcid":null,"position":3,"is_corresponding":false},{"id":138390,"name":"Ernest M. Hannig","orcid":null,"position":4,"is_corresponding":false},{"id":137366,"name":"Gerhard Wagner","orcid":"0000-0002-2063-4401","position":5,"is_corresponding":false},{"id":136559,"name":"Katsura Asano","orcid":null,"position":6,"is_corresponding":false},{"id":138386,"name":"Yasufumi Yamamoto","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.418840607796598,"endowment":4.418840607796598,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16254050","pmcid":"PMC1283452","openalex_id":"https://openalex.org/W2024846833","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA68262","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"1 P20 RR15563","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM064781","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA068262","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01GM64781","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"P20 RR015563","title":null}],"total_grants":6,"fwci":1.6425,"citation_percentile":0.82084588,"influential_citations":7,"citation_trend":[{"year":2012,"count":10},{"year":2013,"count":4},{"year":2014,"count":5},{"year":2015,"count":1},{"year":2016,"count":2},{"year":2017,"count":4},{"year":2018,"count":4},{"year":2020,"count":3},{"year":2021,"count":5},{"year":2022,"count":7},{"year":2023,"count":1},{"year":2024,"count":4},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1283452","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc1283452?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1283452","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0507960102","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0507960102","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16254050","host_type":"repository"}],"fields_of_study":["RNA and protein synthesis mechanisms","Polyamine Metabolism and Applications","RNA regulation and disease","Biology","Medicine","Chemistry","Binding Sites","Eukaryotic Initiation Factor-1","Eukaryotic Initiation Factor-2","Eukaryotic Initiation Factor-3","Eukaryotic Initiation Factor-4G","Eukaryotic Initiation Factor-5","Mutation","Protein Biosynthesis","Protein Structure, Secondary","Protein Structure, Tertiary"],"mesh_terms":["Binding Sites","Mutation","Protein Biosynthesis","Eukaryotic Initiation Factor-2","Eukaryotic Initiation Factor-1","Protein Structure, Secondary","Protein Structure, Tertiary","Eukaryotic Initiation Factor-4G","Eukaryotic Initiation Factor-3","Eukaryotic Initiation Factor-5"],"keywords":["EIF4G","Transcription preinitiation complex","eIF2","Eukaryotic translation","Eukaryotic initiation factor","Cell biology","Initiation factor","Biology","EIF4A1","Eukaryotic translation initiation factor 4 gamma","CTD","Biochemistry","Translation (biology)","Promoter","Messenger RNA"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.19738588.v1","title":"Additional file 1 of Non-AUG translation initiation in mammals","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19738588","title":"Additional file 1 of Non-AUG translation initiation in mammals","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T16:16:22.285331Z","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":[]}