4HT1

Human TWEAK in complex with the Fab fragment of a neutralizing antibody

4HT1 の概要

• エントリーDOI: 10.2210/pdb4ht1/pdb
• 分子名称: Tumor necrosis factor ligand superfamily member 12, chimeric antibody Fab, ... (4 entities in total)
• 機能のキーワード: antibody fab, tnf homology domain, cytokine, tweak receptor, membrane bound, extracellular thd domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane ; Single-pass type II membrane protein . Tumor necrosis factor ligand superfamily member 12, secreted form: Secreted. Isoform TWE-PRIL: Cell membrane; Single-pass membrane protein: O43508
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 64801.81

構造登録者

Lammens, A. (登録日: 2012-10-31, 公開日: 2013-06-12, 最終更新日: 2024-10-30)

主引用文献

Lammens, A.,Baehner, M.,Kohnert, U.,Niewoehner, J.,von Proff, L.,Schraeml, M.,Lammens, K.,Hopfner, K.P.
Crystal Structure of Human TWEAK in Complex with the Fab Fragment of a Neutralizing Antibody Reveals Insights into Receptor Binding.
Plos One, 8:e62697-e62697, 2013

PubMed Abstract: The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine playing a key role in tissue regeneration and remodeling. Dysregulation of TWEAK signaling is involved in various pathological processes like autoimmune diseases and cancer. The unique interaction with its cognate receptor Fn14 makes both ligand and receptor promising targets for novel therapeutics. To gain insights into this important signaling pathway, we determined the structure of soluble human TWEAK in complex with the Fab fragment of an antibody selected for inhibition of receptor binding. In the crystallized complex TWEAK is bound by three Fab fragments of the neutralizing antibody. Homology modeling shows that Fab binding overlaps with the putative Fn14 binding site of TWEAK. Docking of the Fn14 cysteine rich domain (CRD) to that site generates a highly complementary interface with perfectly opposing charged and hydrophobic residues. Taken together the presented structure provides new insights into the biology of TWEAK and the TWEAK/Fn14 pathway, which will help to optimize the therapeutic strategy for treatment of related cancer types and autoimmune diseases.

PubMed: 23667509
DOI: 10.1371/journal.pone.0062697

実験手法

X-RAY DIFFRACTION (2.498 Å)