5DJY

Fc Heterodimer Design 20.8 Y349S/T366V/K370Y/K409V + E357D/S364Q/Y407A

5DJY の概要

• エントリーDOI: 10.2210/pdb5djy/pdb
• 関連するPDBエントリー: 5DI8 5DJ0 5DJ2 5DJ6 5DJ8 5DJA 5DJC 5DJD 5DJX 5DJZ 5DK0 5DK2 5DVK 5DVL 5DVM 5DVN 5DVO
• 分子名称: Ig gamma-1 chain C region, Fc-III peptide, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: heterodimer, immunoglobulin, ch3, fc, bispecific antibody, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted : P01857 P01857
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 56834.47

構造登録者

Atwell, S.,Leaver-Fay, A.,Froning, K.J.,Aldaz, H.,Pustilnik, A.,Lu, F.,Huang, F.,Yuan, R.,Dhanani, S.H.,Chamberlain, A.K.,Fitchett, J.R.,Gutierrez, B.,Hendle, J.,Demarest, S.J.,Kuhlman, B. (登録日: 2015-09-02, 公開日: 2016-03-30, 最終更新日: 2024-10-09)

主引用文献

Leaver-Fay, A.,Froning, K.J.,Atwell, S.,Aldaz, H.,Pustilnik, A.,Lu, F.,Huang, F.,Yuan, R.,Hassanali, S.,Chamberlain, A.K.,Fitchett, J.R.,Demarest, S.J.,Kuhlman, B.
Computationally Designed Bispecific Antibodies using Negative State Repertoires.
Structure, 24:641-651, 2016

PubMed Abstract: A challenge in the structure-based design of specificity is modeling the negative states, i.e., the complexes that you do not want to form. This is a difficult problem because mutations predicted to destabilize the negative state might be accommodated by small conformational rearrangements. To overcome this challenge, we employ an iterative strategy that cycles between sequence design and protein docking in order to build up an ensemble of alternative negative state conformations for use in specificity prediction. We have applied our technique to the design of heterodimeric CH3 interfaces in the Fc region of antibodies. Combining computationally and rationally designed mutations produced unique designs with heterodimer purities greater than 90%. Asymmetric Fc crystallization was able to resolve the interface mutations; the heterodimer structures confirmed that the interfaces formed as designed. With these CH3 mutations, and those made at the heavy-/light-chain interface, we demonstrate one-step synthesis of four fully IgG-bispecific antibodies.

PubMed: 26996964
DOI: 10.1016/j.str.2016.02.013

実験手法

X-RAY DIFFRACTION (2.15 Å)