3EO1

Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3

3EO1 の概要

• エントリーDOI: 10.2210/pdb3eo1/pdb
• 関連するPDBエントリー: 3EO0
• 分子名称: GC-1008 Fab Light Chain, GC-1008 Fab Heavy Chain, Transforming growth factor beta-3 (3 entities in total)
• 機能のキーワード: antibody-cytokine complex, growth factor, fab fragment, cardiomyopathy, cleavage on pair of basic residues, glycoprotein, mitogen, polymorphism, secreted, immune system-cytokine complex, immune system/cytokine
• 由来する生物種: Mus musculus; 詳細
• 細胞内の位置: Secreted: P10600
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 239996.87

構造登録者

Gruetter, C.,Gruetter, M.G. (登録日: 2008-09-26, 公開日: 2008-12-02, 最終更新日: 2024-10-09)

主引用文献

Wilkinson, T.,Turner, R.,Podichetty, S.,Finch, D.,McCourt, M.,Loning, S.,Jermutus, L.
A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions
Proc.Natl.Acad.Sci.Usa, 105:20251-20256, 2008

PubMed Abstract: TGF-beta isoforms are key modulators of a broad range of biological pathways and increasingly are exploited as therapeutic targets. Here, we describe the crystal structures of a pan-TGF-beta neutralizing antibody, GC-1008, alone and in complex with TGF-beta3. The antibody is currently in clinical evaluation for idiopathic pulmonary fibrosis, melanoma, and renal cell cancer. GC-1008 recognizes an asymmetric binding interface across the TGF-beta homodimer with high affinity. Whereas both cognate receptors, TGF-beta-receptor types I and II, are required to recognize all 3 TGF-beta isoforms, GC-1008 has been engineered to bind with high affinity to TGF-beta1, 2, and 3 via a single interaction surface. Comparison with existing structures and models of TGF-beta interaction with its receptors suggests that the antibody binds to a similar epitope to the 2 receptors together and is therefore a structurally different but functionally identical mimic of the binding mode of both receptors.

PubMed: 19073914
DOI: 10.1073/pnas.0807200106

実験手法

X-RAY DIFFRACTION (3.1 Å)