7LUS

IgG2 Fc Charge Pair Mutation version 1 (CPMv1)

7LUS の概要

• エントリーDOI: 10.2210/pdb7lus/pdb
• 分子名称: Immunoglobulin heavy constant gamma 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]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, ... (4 entities in total)
• 機能のキーワード: fragment crystallizable, fc, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50161.05

構造登録者

Sudom, A.,Whittington, D.,Garces, F.,Wang, Z. (登録日: 2021-02-23, 公開日: 2021-09-15, 最終更新日: 2024-11-20)

主引用文献

Estes, B.,Sudom, A.,Gong, D.,Whittington, D.A.,Li, V.,Mohr, C.,Li, D.,Riley, T.P.,Shi, S.D.,Zhang, J.,Garces, F.,Wang, Z.
Next generation Fc scaffold for multispecific antibodies.
Iscience, 24:103447-103447, 2021

PubMed Abstract: Bispecific antibodies (Bispecifics) demonstrate exceptional clinical potential to address some of the most complex diseases. However, Bispecific production in a single cell often requires the correct pairing of multiple polypeptide chains for desired assembly. This is a considerable hurdle that hinders the development of many immunoglobulin G (IgG)-like bispecific formats. Our approach focuses on the rational engineering of charged residues to facilitate the chain pairing of distinct heavy chains (HC). Here, we deploy structure-guided protein design to engineer charge pair mutations (CPMs) placed in the CH3-CH3' interface of the fragment crystallizable (Fc) region of an antibody (Ab) to correctly steer heavy chain pairing. When used in combination with our stable effector functionless 2 (SEFL2.2) technology, we observed high pairing efficiency without significant losses in expression yields. Furthermore, we investigate the relationship between CPMs and the sequence diversity in the parental antibodies, proposing a rational strategy to deploy these engineering technologies.

PubMed: 34877503
DOI: 10.1016/j.isci.2021.103447

実験手法

X-RAY DIFFRACTION (2.45 Å)