2RJK

Crystal Structure of Human TL1A Extracellular Domain C95S Mutant

2RJK の概要

• エントリーDOI: 10.2210/pdb2rjk/pdb
• 関連するPDBエントリー: 2QE3 2RJL
• 分子名称: TNF superfamily ligand TL1A (2 entities in total)
• 機能のキーワード: tl1a, tnfsf, cytokine, mutant, membrane, transmembrane
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20893.68

構造登録者

Zhan, C.,Yan, Q.,Patskovsky, Y.,Shi, W.,Ramagopal, U.A.,Toro, R.,Bonanno, J.,Nathenson, S.G.,Almo, S.C. (登録日: 2007-10-15, 公開日: 2008-08-26, 最終更新日: 2023-08-30)

主引用文献

Zhan, C.,Yan, Q.,Patskovsky, Y.,Li, Z.,Toro, R.,Meyer, A.,Cheng, H.,Brenowitz, M.,Nathenson, S.G.,Almo, S.C.
Biochemical and structural characterization of the human TL1A ectodomain.
Biochemistry, 48:7636-7645, 2009

PubMed Abstract: TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 A, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3 differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors.

PubMed: 19522538
DOI: 10.1021/bi900031w

実験手法

X-RAY DIFFRACTION (2.3 Å)