6FXN

Crystal structure of human BAFF in complex with Fab fragment of anti-BAFF antibody belimumab

「6ERX」から置き換えられました

6FXN の概要

• エントリーDOI: 10.2210/pdb6fxn/pdb
• 分子名称: Tumor necrosis factor ligand superfamily member 13B, belimumab heavy chain, belimumab light chain, ... (4 entities in total)
• 機能のキーワード: immunology, b cell, cytokine, baff, antibody, proteros, 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 13b, soluble form: Secreted: Q9Y275
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 389186.91

構造登録者

Lammens, A.,Maskos, K.,Willen, L.,Jiang, X.,Schneider, P. (登録日: 2018-03-09, 公開日: 2018-04-04, 最終更新日: 2024-11-20)

主引用文献

Vigolo, M.,Chambers, M.G.,Willen, L.,Chevalley, D.,Maskos, K.,Lammens, A.,Tardivel, A.,Das, D.,Kowalczyk-Quintas, C.,Schuepbach-Mallepell, S.,Smulski, C.R.,Eslami, M.,Rolink, A.,Hummler, E.,Samy, E.,Fomekong Nanfack, Y.,Mackay, F.,Liao, M.,Hess, H.,Jiang, X.,Schneider, P.
A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors.
Nat Commun, 9:1199-1199, 2018

PubMed Abstract: The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and is targeted in the clinic for the treatment of systemic lupus erythematosus. BAFF contains a loop region designated the flap, which is dispensable for receptor binding. Here we show that the flap of BAFF has two functions. In addition to facilitating the formation of a highly active BAFF 60-mer as shown previously, it also converts binding of BAFF to TNFRSF13C (BAFFR) into a signaling event via oligomerization of individual BAFF-BAFFR complexes. Binding and activation of BAFFR can therefore be targeted independently to inhibit or activate the function of BAFF. Moreover, structural analyses suggest that the flap of BAFF 60-mer temporarily prevents binding of an anti-BAFF antibody (belimumab) but not of a decoy receptor (atacicept). The observed differences in profiles of BAFF inhibition may confer distinct biological and clinical efficacies to these therapeutically relevant inhibitors.

PubMed: 29572442
DOI: 10.1038/s41467-018-03323-8

実験手法

X-RAY DIFFRACTION (2.9 Å)