4Z5R

Rontalizumab Fab bound to Interferon-a2

4Z5R の概要

• エントリーDOI: 10.2210/pdb4z5r/pdb
• 分子名称: Interferon alpha-2, anti-IFN-a antibody rontalizumab light chain, anti-IFN-a antibody rontalizumab heavy chain modules VH and CH1 (Fab), ... (4 entities in total)
• 機能のキーワード: antibody, interferon, cytokine-immune system complex, cytokine/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted: P01563
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 540246.16

構造登録者

Eigenbrot, C.,Maurer, B.,Bosanac, I. (登録日: 2015-04-02, 公開日: 2015-07-08, 最終更新日: 2024-10-09)

主引用文献

Maurer, B.,Bosanac, I.,Shia, S.,Kwong, M.,Corpuz, R.,Vandlen, R.,Schmidt, K.,Eigenbrot, C.
Structural basis of the broadly neutralizing anti-interferon-alpha antibody rontalizumab.
Protein Sci., 24:1440-1450, 2015

PubMed Abstract: Interferons-alpha (IFN-α) are the expressed gene products comprising thirteen type I interferons with protein pairwise sequence similarities in the 77-96% range. Three other widely expressed human type I interferons, IFN-β, IFN-κ and IFN-ω have sequences 29-33%, 29-32% and 56-60% similar to the IFN-αs, respectively. Type I interferons act on immune cells by producing subtly different immune-modulatory effects upon binding to the extracellular domains of a heterodimeric cell-surface receptor composed of IFNAR1 and IFNAR2, most notably anti-viral effects. IFN-α has been used to treat infection by hepatitis-virus type C (HCV) and a correlation between hyperactivity of IFN-α-induced signaling and systemic lupus erythematosis (SLE), or lupus, has been noted. Anti-IFN-α antibodies including rontalizumab have been under clinical study for the treatment of lupus. To better understand the rontalizumab mechanism of action and specificity, we determined the X-ray crystal structure of the Fab fragment of rontalizumab bound to human IFN-α2 at 3Å resolution and find substantial overlap of the antibody and IFNA2 epitopes on IFN-α2.

PubMed: 26099203
DOI: 10.1002/pro.2729

実験手法

X-RAY DIFFRACTION (3 Å)