Conformational effects of N-glycan core fucosylation of immunoglobulin G fc region on its interaction with Fcgamma receptor IIIa
書誌事項
- タイトル別名
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- Conformational effects of N-glycan core fucosylation of immunoglobulin G Fc region on its interaction with Fcγ receptor IIIa
抄録
Antibody-dependent cellular cytotoxicity (ADCC) is promoted through interaction between the Fc region of immunoglobulin G1 (IgG1) and Fcγ receptor IIIa (FcγRIIIa), 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 FcγRIIIa (sFcγRIIIa) in complex with IgG1-Fc. Our simulation highlights increased conformational fluctuation of the N-glycan at Asn162 of sFcγRIIIa 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 sFcγRIIIa 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 sFcγRIIIa without Fc core fucosylation. Our findings offer a structural foundation for designing and developing therapeutic antibodies with improved ADCC activity.
収録刊行物
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- Scientific Reports
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Scientific Reports 7 (1), 13780-, 2017-11
Springer Nature
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詳細情報 詳細情報について
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- CRID
- 1050282813790513024
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- NII論文ID
- 120006545940
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- ISSN
- 20452322
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- HANDLE
- 2237/00029165
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- Crossref
- CiNii Articles
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