Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans
-
- Tsunehiro Mizushima
- Graduate School of Pharmaceutical Sciences, Nagoya City University, 3‐1 Tanabe‐dori, Mizuho‐ku, Nagoya 467‐8603, Japan
-
- Hirokazu Yagi
- Graduate School of Pharmaceutical Sciences, Nagoya City University, 3‐1 Tanabe‐dori, Mizuho‐ku, Nagoya 467‐8603, Japan
-
- Emi Takemoto
- Graduate School of Pharmaceutical Sciences, Nagoya City University, 3‐1 Tanabe‐dori, Mizuho‐ku, Nagoya 467‐8603, Japan
-
- Mami Shibata‐Koyama
- Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd, 3‐6‐6 Asahi‐machi, Machida‐shi, Tokyo 194‐8533, Japan
-
- Yuya Isoda
- Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd, 3‐6‐6 Asahi‐machi, Machida‐shi, Tokyo 194‐8533, Japan
-
- Shigeru Iida
- Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd, 3‐6‐6 Asahi‐machi, Machida‐shi, Tokyo 194‐8533, Japan
-
- Kazuhiro Masuda
- Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd, 3‐6‐6 Asahi‐machi, Machida‐shi, Tokyo 194‐8533, Japan
-
- Mitsuo Satoh
- Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd, 3‐6‐6 Asahi‐machi, Machida‐shi, Tokyo 194‐8533, Japan
-
- Koichi Kato
- Graduate School of Pharmaceutical Sciences, Nagoya City University, 3‐1 Tanabe‐dori, Mizuho‐ku, Nagoya 467‐8603, Japan
説明
Removal of the fucose residue from the N-glycans of the Fc portion of immunoglobulin G (IgG) results in a dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) through improved affinity for Fcγ receptor IIIa (FcγRIIIa). Here, we present the 2.2-Å structure of the complex formed between nonfucosylated IgG1-Fc and a soluble form of FcγRIIIa (sFcγRIIIa) with two N-glycosylation sites. The crystal structure shows that one of the two N-glycans of sFcγRIIIa mediates the interaction with nonfucosylated Fc, thereby stabilizing the complex. However, fucosylation of the Fc N-glycans inhibits this interaction, because of steric hindrance, and furthermore, negatively affects the dynamics of the receptor binding site. Our results offer a structural basis for improvement in ADCC of therapeutic antibodies by defucosylation.
収録刊行物
-
- Genes to Cells
-
Genes to Cells 16 (11), 1071-1080, 2011-10-02
Wiley
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1360285710544807552
-
- ISSN
- 13652443
- 13569597
-
- PubMed
- 22023369
-
- Web Site
- https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1365-2443.2011.01552.x
- https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2443.2011.01552.x
- https://onlinelibrary.wiley.com/doi/full-xml/10.1111/j.1365-2443.2011.01552.x
- http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1365-2443.2011.01552.x/fullpdf
-
- 資料種別
- journal article
-
- データソース種別
-
- Crossref
- KAKEN
- OpenAIRE
