6GFE

High-resolution Structure of a therapeutic full-length anti-NPRA Antibody with exceptional Conformational Diversity

6GFE の概要

• エントリーDOI: 10.2210/pdb6gfe/pdb
• 分子名称: Immunoglobulin gamma-4 heavy chain, Immunoglobulin gamma-4 light chain, 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, ... (6 entities in total)
• 機能のキーワード: immunoglobulin, antibody, natriuretic peptide receptor a, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 149267.04

構造登録者

Hoerer, S. (登録日: 2018-04-30, 公開日: 2019-05-15, 最終更新日: 2024-10-16)

主引用文献

Blech, M.,Horer, S.,Kuhn, A.B.,Kube, S.,Goddeke, H.,Kiefer, H.,Zang, Y.,Alber, Y.,Kast, S.M.,Westermann, M.,Tully, M.D.,Schafer, L.V.,Garidel, P.
Structure of a Therapeutic Full-Length Anti-NPRA IgG4 Antibody: Dissecting Conformational Diversity.
Biophys.J., 116:1637-1649, 2019

PubMed Abstract: We report the x-ray crystal structure of intact, full-length human immunoglobulin (IgG4) at 1.8 Å resolution. The data for IgG4 (S228P), an antibody targeting the natriuretic peptide receptor A, show a previously unrecognized type of Fab-Fc orientation with a distorted λ-shape in which one Fab-arm is oriented toward the Fc portion. Detailed structural analysis by x-ray crystallography and molecular simulations suggest that this is one of several conformations coexisting in a dynamic equilibrium state. These results were confirmed by small angle x-ray scattering in solution. Furthermore, electron microscopy supported these findings by preserving molecule classes of different conformations. This study fosters our understanding of IgG4 in particular and our appreciation of antibody flexibility in general. Moreover, we give insights into potential biological implications, specifically for the interaction of human anti-natriuretic peptide receptor A IgG4 with the neonatal Fc receptor, Fcγ receptors, and complement-activating C1q by considering conformational flexibility.

PubMed: 31023536
DOI: 10.1016/j.bpj.2019.03.036

実験手法

X-RAY DIFFRACTION (1.8 Å)