6WNA

Next generation monomeric IgG4 Fc

6WNA の概要

• エントリーDOI: 10.2210/pdb6wna/pdb
• 分子名称: IgG receptor FcRn large subunit p51, Beta-2-microglobulin, Immunoglobulin heavy constant gamma 4, ... (5 entities in total)
• 機能のキーワード: antibody constant region, fragment crystallizable, mutated, immune system, neonatal receptor interaction, half-life
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 66595.43

構造登録者

Oganesyan, V.Y.,Shan, L.,van Dyk, N.,Dall'Acqua, W.F. (登録日: 2020-04-22, 公開日: 2021-09-15, 最終更新日: 2024-10-16)

主引用文献

Shan, L.,Dyk, N.V.,Haskins, N.,Cook, K.M.,Rosenthal, K.L.,Mazor, R.,Dragulin-Otto, S.,Jiang, Y.,Wu, H.,Dall'Acqua, W.F.,Borrok, M.J.,Damschroder, M.M.,Oganesyan, V.
In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance.
Commun Biol, 4:1048-1048, 2021

PubMed Abstract: In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life.

PubMed: 34497355
DOI: 10.1038/s42003-021-02565-5

実験手法

X-RAY DIFFRACTION (2.4 Å)