{"created":"2023-06-26T11:02:04.891608+00:00","id":2852,"links":{},"metadata":{"_buckets":{"deposit":"ba90939b-87d7-4dd8-be69-9b926879a69d"},"_deposit":{"created_by":31,"id":"2852","owners":[31],"pid":{"revision_id":0,"type":"depid","value":"2852"},"status":"published"},"_oai":{"id":"oai:oist.repo.nii.ac.jp:00002852","sets":["6:42","6:57"]},"author_link":["18225","18221","18222","18224","18227","18226","18223"],"item_10001_biblio_info_7":{"attribute_name":"Bibliographic Information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-11-30","bibliographicIssueDateType":"Issued"},"bibliographicVolumeNumber":"13","bibliographic_titles":[{},{"bibliographic_title":"Frontiers in Endocrinology","bibliographic_titleLang":"en"}]}]},"item_10001_creator_3":{"attribute_name":"Author","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Purba, Endang R."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Saita, Ei-ichiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Akhouri, Reetesh R."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Öfverstedt, Lars-Goran"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Wilken, Gunnar"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Skoglund, Ulf"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Maruyama, Ichiro N."}],"nameIdentifiers":[{}]}]},"item_10001_description_5":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Aberrant activation of the epidermal growth factor receptor (EGFR) by mutations has been implicated in a variety of human cancers. Elucidation of the structure of the full-length receptor is essential to understand the molecular mechanisms underlying its activation. Unlike previously anticipated, here, we report that purified full-length EGFR adopts a homodimeric form in vitro before and after ligand binding. Cryo-electron tomography analysis of the purified receptor also showed that the extracellular domains of the receptor dimer, which are conformationally flexible before activation, are stabilized by ligand binding. This conformational flexibility stabilization most likely accompanies rotation of the entire extracellular domain and the transmembrane domain, resulting in dissociation of the intracellular kinase dimer and, thus, rearranging it into an active form. Consistently, mutations of amino acid residues at the interface of the symmetric inactive kinase dimer spontaneously activate the receptor in vivo. Optical observation also indicated that binding of only one ligand activates the receptor dimer on the cell surface. Our results suggest how oncogenic mutations spontaneously activate the receptor and shed light on the development of novel cancer therapies.","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"Publisher","attribute_value_mlt":[{"subitem_publisher":"Frontiers Media S.A."}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.3389/fendo.2022.1042787","subitem_relation_type_select":"DOI"}}]},"item_10001_relation_17":{"attribute_name":"Related site","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://www.frontiersin.org/articles/10.3389/fendo.2022.1042787/full","subitem_relation_type_select":"URI"}}]},"item_10001_rights_15":{"attribute_name":"Rights","attribute_value_mlt":[{"subitem_rights":"© 2022 © 2022 Purba, Saita, Akhouri, Öfverstedt, Wilken, Skoglund and Maruyama."}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1664-2392","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"Author's flag","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-12-01"}],"displaytype":"detail","filename":"fendo-13-1042787.pdf","filesize":[{"value":"9.7 MB"}],"format":"application/pdf","license_note":"CC BY 4.0\nCreative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/)","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"fendo-13-1042787","url":"https://oist.repo.nii.ac.jp/record/2852/files/fendo-13-1042787.pdf"},"version_id":"8a07f9b2-93c8-4fae-957c-7e6a4f95a8dc"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"cancer biology","subitem_subject_scheme":"Other"},{"subitem_subject":"conformational change","subitem_subject_scheme":"Other"},{"subitem_subject":"cooperativity","subitem_subject_scheme":"Other"},{"subitem_subject":"cryo-electron tomography","subitem_subject_scheme":"Other"},{"subitem_subject":"receptor tyrosine kinase","subitem_subject_scheme":"Other"},{"subitem_subject":"signal transduction","subitem_subject_scheme":"Other"},{"subitem_subject":"single-molecule biophysics","subitem_subject_scheme":"Other"},{"subitem_subject":"transmembrane signaling","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Allosteric activation of preformed EGF receptor dimers by a single ligand binding event","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Allosteric activation of preformed EGF receptor dimers by a single ligand binding event"}]},"item_type_id":"10001","owner":"31","path":["42","57"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-12-01"},"publish_date":"2022-12-01","publish_status":"0","recid":"2852","relation_version_is_last":true,"title":["Allosteric activation of preformed EGF receptor dimers by a single ligand binding event"],"weko_creator_id":"31","weko_shared_id":31},"updated":"2023-06-26T11:22:30.835169+00:00"}