{"created":"2021-03-01T06:34:55.725103+00:00","id":26962,"links":{},"metadata":{"_buckets":{"deposit":"dfa3a787-dad5-409e-bc97-041f6e259ecd"},"_deposit":{"id":"26962","owners":[],"pid":{"revision_id":0,"type":"depid","value":"26962"},"status":"published"},"_oai":{"id":"oai:nagoya.repo.nii.ac.jp:00026962"},"item_10_biblio_info_6":{"attribute_name":"\u66f8\u8a8c\u60c5\u5831","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-11","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageStart":"13780","bibliographicVolumeNumber":"7","bibliographic_titles":[{"bibliographic_title":"Scientific Reports"}]}]},"item_10_description_4":{"attribute_name":"\u6284\u9332","attribute_value_mlt":[{"subitem_description":"Antibody-dependent cellular cytotoxicity (ADCC) is promoted through interaction between the Fc region of immunoglobulin G1 (IgG1) and Fc\u03b3 receptor IIIa (Fc\u03b3RIIIa), depending on N-glycosylation of these glycoproteins. In particular, core fucosylation of IgG1-Fc N-glycans negatively affects this interaction and thereby compromises ADCC activity. To address the mechanisms of this effect, we performed replica-exchange molecular dynamics simulations based on crystallographic analysis of a soluble form of Fc\u03b3RIIIa (sFc\u03b3RIIIa) in complex with IgG1-Fc. Our simulation highlights increased conformational fluctuation of the N-glycan at Asn162 of sFc\u03b3RIIIa upon fucosylation of IgG1-Fc, consistent with crystallographic data giving no interpretable electron density for this N-glycan, except for the innermost part. The fucose residue disrupts optimum intermolecular carbohydrate-carbohydrate interactions, rendering this sFc\u03b3RIIIa glycan distal from the Fc glycan. Moreover, our simulation demonstrates that core fucosylation of IgG1-Fc affects conformational dynamics and rearrangements of surrounding amino acid residues, typified by Tyr296 of IgG1-Fc, which was more extensively involved in the interaction with sFc\u03b3RIIIa without Fc core fucosylation. Our findings offer a structural foundation for designing and developing therapeutic antibodies with improved ADCC activity.","subitem_description_type":"Abstract"}]},"item_10_publisher_32":{"attribute_name":"\u51fa\u7248\u8005","attribute_value_mlt":[{"subitem_publisher":"Springer Nature"}]},"item_10_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1038/s41598-017-13845-8","subitem_relation_type_select":"DOI"}}]},"item_10_rights_12":{"attribute_name":"\u6a29\u5229","attribute_value_mlt":[{"subitem_rights":"This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article\u2019s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/."}]},"item_10_select_15":{"attribute_name":"\u8457\u8005\u7248\u30d5\u30e9\u30b0","attribute_value_mlt":[{"subitem_select_item":"publisher"}]},"item_10_source_id_62":{"attribute_name":"ISSN\uff08Online\uff09","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"\u8457\u8005","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Sakae, Yoshitake"}],"nameIdentifiers":[{"nameIdentifier":"88330","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Satoh, Tadashi"}],"nameIdentifiers":[{"nameIdentifier":"88331","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yagi, Hirokazu"}],"nameIdentifiers":[{"nameIdentifier":"88332","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yanaka, Saeko"}],"nameIdentifiers":[{"nameIdentifier":"88333","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamaguchi, Takumi"}],"nameIdentifiers":[{"nameIdentifier":"88334","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Isoda, Yuya"}],"nameIdentifiers":[{"nameIdentifier":"88335","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Iida, Shigeru"}],"nameIdentifiers":[{"nameIdentifier":"88336","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okamoto, Yuko"}],"nameIdentifiers":[{"nameIdentifier":"88337","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kato, Koichi"}],"nameIdentifiers":[{"nameIdentifier":"88338","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"\u30d5\u30a1\u30a4\u30eb\u60c5\u5831","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-12-26"}],"displaytype":"detail","filename":"s41598-017-13845-8.pdf","filesize":[{"value":"2.4 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"s41598-017-13845-8","url":"https://nagoya.repo.nii.ac.jp/record/26962/files/s41598-017-13845-8.pdf"},"version_id":"74de6d78-88fa-4bd8-a3f9-addabac832e0"}]},"item_language":{"attribute_name":"\u8a00\u8a9e","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"\u8cc7\u6e90\u30bf\u30a4\u30d7","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Conformational effects of N-glycan core fucosylation of immunoglobulin G Fc region on its interaction with Fc\u03b3 receptor IIIa","item_titles":{"attribute_name":"\u30bf\u30a4\u30c8\u30eb","attribute_value_mlt":[{"subitem_title":"Conformational effects of N-glycan core fucosylation of immunoglobulin G Fc region on its interaction with Fc\u03b3 receptor IIIa"}]},"item_type_id":"10","owner":"1","path":["336/695/696"],"pubdate":{"attribute_name":"\u516c\u958b\u65e5","attribute_value":"2018-12-26"},"publish_date":"2018-12-26","publish_status":"0","recid":"26962","relation_version_is_last":true,"title":["Conformational effects of N-glycan core fucosylation of immunoglobulin G Fc region on its interaction with Fc\u03b3 receptor IIIa"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2021-03-01T10:47:51.179525+00:00"}