5L36

Crystal Structure of a human FasL mutant in complex with human DcR3

5L36 の概要

• エントリーDOI: 10.2210/pdb5l36/pdb
• 関連するPDBエントリー: 4MSV 5L19
• 分子名称: Tumor necrosis factor receptor superfamily member 6B, Tumor necrosis factor ligand superfamily member 6, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: fasl, cd95l, dcr3, tnf ligand and receptor, decoy receptor, apoptosis
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36516.36

構造登録者

Liu, W.,Bonanno, J.B.,Almo, S.C. (登録日: 2016-08-03, 公開日: 2016-09-07, 最終更新日: 2024-10-23)

主引用文献

Liu, W.,Ramagopal, U.,Cheng, H.,Bonanno, J.B.,Toro, R.,Bhosle, R.,Zhan, C.,Almo, S.C.
Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.
Structure, 24:2016-2023, 2016

PubMed Abstract: The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3.

PubMed: 27806260
DOI: 10.1016/j.str.2016.09.009

実験手法

X-RAY DIFFRACTION (3.1 Å)