4GRW

Structure of a complex of human IL-23 with 3 Nanobodies (Llama vHHs)

4GRW の概要

• エントリーDOI: 10.2210/pdb4grw/pdb
• 分子名称: Interleukin-23 subunit alpha, Interleukin-12 subunit beta, Nanobody 124C4, ... (7 entities in total)
• 機能のキーワード: cytokine, immunoglobulin fold, vhh domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 199002.13

構造登録者

Desmyter, A.,Spinelli, S.,Button, C.,Saunders, M.,de Haard, H.,Rommelaere, H.,Union, A.,Cambillau, C. (登録日: 2012-08-27, 公開日: 2014-02-19, 最終更新日: 2024-10-30)

主引用文献

Desmyter, A.,Spinelli, S.,Boutton, C.,Saunders, M.,Blachetot, C.,de Haard, H.,Denecker, G.,Van Roy, M.,Cambillau, C.,Rommelaere, H.
Neutralization of Human Interleukin 23 by Multivalent Nanobodies Explained by the Structure of Cytokine-Nanobody Complex.
Front Immunol, 8:884-884, 2017

PubMed Abstract: The heterodimeric cytokine interleukin (IL) 23 comprises the IL12-shared p40 subunit and an IL23-specific subunit, p19. Together with IL12 and IL27, IL23 sits at the apex of the regulatory mechanisms shaping adaptive immune responses. IL23, together with IL17, plays an important role in the development of chronic inflammation and autoimmune inflammatory diseases. In this context, we generated monovalent antihuman IL23 variable heavy chain domain of llama heavy chain antibody (V) domains (Nanobodies) with low nanomolar affinity for human interleukin (hIL) 23. The crystal structure of a quaternary complex assembling hIL23 and several nanobodies against p19 and p40 subunits allowed identification of distinct epitopes and enabled rational design of a multivalent IL23-specific blocking nanobody. Taking advantage of the ease of nanobody formatting, multivalent IL23 nanobodies were assembled with properly designed linkers flanking an antihuman serum albumin nanobody, with improved hIL23 neutralization capacity and , as compared to the monovalent nanobodies. These constructs with long exposure time are excellent candidates for further developments targeting Crohn's disease, rheumatoid arthritis, and psoriasis.

PubMed: 28871249
DOI: 10.3389/fimmu.2017.00884

実験手法

X-RAY DIFFRACTION (2.55 Å)