4EOW

Crystal structure of a disease-associated anti-human GM-CSF autoantibody MB007

4EOW の概要

• エントリーDOI: 10.2210/pdb4eow/pdb
• 分子名称: MB007 human IgG1 Fab fragment heavy chain, MB007 IgG1 Fab fragment light chain (3 entities in total)
• 機能のキーワード: immunsystem, alpha-helical stretch in cdr3-h, protein-docking, immunoglobulin igg1 (lambda), autoantibody causing pap, gm-csf, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted : P0DOY2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47541.88

構造登録者

Blech, M. (登録日: 2012-04-16, 公開日: 2012-08-22, 最終更新日: 2024-10-09)

主引用文献

Blech, M.,Seeliger, D.,Kistler, B.,Bauer, M.M.,Hafner, M.,Horer, S.,Zeeb, M.,Nar, H.,Park, J.E.
Molecular structure of human GM-CSF in complex with a disease-associated anti-human GM-CSF autoantibody and its potential biological implications.
Biochem.J., 447:205-215, 2012

PubMed Abstract: Polyclonal autoantibodies against human GM-CSF (granulocyte/macrophage colony-stimulating factor) are a hallmark of PAP (pulmonary alveolar proteinosis) and several other reported autoimmune diseases. MB007 is a high-affinity anti-(human GM-CSF) autoantibody isolated from a patient suffering from PAP which shows only modest neutralization of GM-CSF bioactivity. We describe the first crystal structure of a cytokine-directed human IgG1λ autoantibody-binding fragment (Fab) at 1.9 Å (1 Å=0.1 nm) resolution. Its CDR3-H substantially differs from all VH7 germline IgG1 structures reported previously. We derive a reliable model of the antigen-autoantibody complex by using NMR chemical shift perturbation data in combination with computational methods. Superposition of the modelled complex structure with the human GM-CSF-GM-CSF ternary receptor complex reveals only little overlap between receptor and Fab when bound to GM-CSF. Our model provides a structural basis for understanding the mode of action of the MB007 autoantibody.

PubMed: 22839360
DOI: 10.1042/BJ20120884

実験手法

X-RAY DIFFRACTION (1.97 Å)