{"doi":"10.1126/science.aaw4104","title":"Structural basis for eIF2B inhibition in integrated stress response","abstract":"<jats:title>Integrated stress response on the brain</jats:title>\n                  <jats:p>\n                    During translation, regulation of protein synthesis by phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is a common consequence of diverse stress stimuli, which leads to reprogramming of gene expression. This process, known as the integrated stress response, is one of the most fundamental mechanisms of translational control conserved throughout eukaryotes. It is also a promising therapeutic target in neurodegenerative diseases and traumatic brain injury. Kashiwagi\n                    <jats:italic>et al.</jats:italic>\n                    report the cryo–electron microscopy and crystal structures and Kenner\n                    <jats:italic>et al.</jats:italic>\n                    report the cryo–electron microscopy structure of the guanine nucleotide exchange factor eIF2B in complex with eIF2 or phosphorylated eIF2. The structures of the eIF2•eIF2B complex reveal that the single phosphorylation modification on eIF2 changes how eIF2 binds to eIF2B and locks this enzyme into an inhibited complex.\n                  </jats:p>\n                  <jats:p>\n                    <jats:italic>Science</jats:italic>\n                    , this issue p.\n                    <jats:related-article xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" issue=\"6439\" page=\"495\" related-article-type=\"in-this-issue\" vol=\"364\" xlink:href=\"10.1126/science.aaw4104\">495</jats:related-article>\n                    , p.\n                    <jats:related-article xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" issue=\"6439\" page=\"491\" related-article-type=\"in-this-issue\" vol=\"364\" xlink:href=\"10.1126/science.aaw2922\">491</jats:related-article>\n                  </jats:p>","journal":"Science","year":2019,"id":635584,"datarank":0.7390880527735809,"base_score":4.927253685157205,"endowment":4.927253685157205,"self_citation_contribution":0.7390880527735809,"citation_network_contribution":0.0,"self_endowment_contribution":0.7390880527735809,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":137,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":587064,"name":"Takeshi Yokoyama","orcid":"0000-0002-0299-9140","position":1,"is_corresponding":false},{"id":554460,"name":"Madoka Nishimoto","orcid":"0000-0003-0948-2504","position":2,"is_corresponding":false},{"id":287606,"name":"Mari Takahashi","orcid":"0000-0002-9995-0019","position":3,"is_corresponding":false},{"id":554459,"name":"Ayako Sakamoto","orcid":"0000-0002-9040-429X","position":4,"is_corresponding":false},{"id":555214,"name":"Mayumi Yonemochi","orcid":null,"position":5,"is_corresponding":false},{"id":554461,"name":"Mikako Shirouzu","orcid":"0000-0002-7997-2149","position":6,"is_corresponding":false},{"id":287609,"name":"Takuhiro Ito","orcid":"0000-0003-3704-5205","position":7,"is_corresponding":false},{"id":554456,"name":"Kazuhiro Kashiwagi","orcid":"0000-0001-6470-5817","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structural basis for eIF2B inhibition in integrated stress response","abstract":"<jats:title>Integrated stress response on the brain</jats:title>\n                  <jats:p>\n                    During translation, regulation of protein synthesis by phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is a common consequence of diverse stress stimuli, which leads to reprogramming of gene expression. This process, known as the integrated stress response, is one of the most fundamental mechanisms of translational control conserved throughout eukaryotes. It is also a promising therapeutic target in neurodegenerative diseases and traumatic brain injury. Kashiwagi\n                    <jats:italic>et al.</jats:italic>\n                    report the cryo–electron microscopy and crystal structures and Kenner\n                    <jats:italic>et al.</jats:italic>\n                    report the cryo–electron microscopy structure of the guanine nucleotide exchange factor eIF2B in complex with eIF2 or phosphorylated eIF2. The structures of the eIF2•eIF2B complex reveal that the single phosphorylation modification on eIF2 changes how eIF2 binds to eIF2B and locks this enzyme into an inhibited complex.\n                  </jats:p>\n                  <jats:p>\n                    <jats:italic>Science</jats:italic>\n                    , this issue p.\n                    <jats:related-article xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" issue=\"6439\" page=\"495\" related-article-type=\"in-this-issue\" vol=\"364\" xlink:href=\"10.1126/science.aaw4104\">495</jats:related-article>\n                    , p.\n                    <jats:related-article xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" issue=\"6439\" page=\"491\" related-article-type=\"in-this-issue\" vol=\"364\" xlink:href=\"10.1126/science.aaw2922\">491</jats:related-article>\n                  </jats:p>","is_dataset_classified":null,"base_score":4.927253685157205,"endowment":4.927253685157205,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31048492","pmcid":null,"openalex_id":"https://openalex.org/W2906537904","authors":[],"funders":[{"funder_name":"Japan Agency for Medical Research and Development","grant_id":"JP18am0101082","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"JP15H01548","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"JP17H05677","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"JP16H04756","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"JP18K14644","title":null},{"funder_name":"Takeda Science Foundation","grant_id":"","title":null}],"total_grants":6,"fwci":5.6168,"citation_percentile":0.97136948,"influential_citations":0,"citation_trend":[{"year":2018,"count":1},{"year":2019,"count":9},{"year":2020,"count":21},{"year":2021,"count":26},{"year":2022,"count":17},{"year":2023,"count":18},{"year":2024,"count":17},{"year":2025,"count":17},{"year":2026,"count":11}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://syndication.highwire.org/content/doi/10.1126/science.aaw4104","host_type":"publisher"},{"url":"https://www.science.org/doi/pdf/10.1126/science.aaw4104","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.aaw4104","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31048492","host_type":"repository"}],"fields_of_study":["RNA regulation and disease","RNA and protein synthesis mechanisms","RNA Research and Splicing","Amino Acid Motifs","Cryoelectron Microscopy","Eukaryotic Initiation Factor-2","Eukaryotic Initiation Factor-2B","Humans","Phosphorylation","Stress, Physiological"],"mesh_terms":["Humans","Phosphorylation","Stress, Physiological","Eukaryotic Initiation Factor-2","Cryoelectron Microscopy","Eukaryotic Initiation Factor-2B","Amino Acid Motifs"],"keywords":["eIF2","Integrated stress response","Eukaryotic translation","Cell biology","Guanine nucleotide exchange factor","Translation (biology)","Phosphorylation","Eukaryotic initiation factor","Biology","Translational regulation","Biochemistry","Signal transduction","Gene","Messenger RNA"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T15:19:01.842161Z","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":[]}