5MJ3

INTERLEUKIN-23 COMPLEX WITH AN ANTAGONISTIC ALPHABODY, CRYSTAL FORM 1

「4OE8」から置き換えられました

5MJ3 の概要

• エントリーDOI: 10.2210/pdb5mj3/pdb
• 分子名称: Interleukin-12 subunit beta, Interleukin-23 subunit alpha, ALPHABODY MA12, ... (8 entities in total)
• 機能のキーワード: designed antiparallel triple-helix coiled-coil, alphabody, immunoglobulin domain, 4-helical bundle cytokine, antagonist, n-linked glycosylation, alkylation, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 67949.25

構造登録者

Desmet, J.,Verstraete, K.,Bloch, Y.,Lorent, E.,Wen, Y.,Devreese, B.,Vandenbroucke, K.,Loverix, S.,Hettmann, T.,Deroo, S.,Somers, K.,Hendrikx, P.,Lasters, I.,Savvides, S.N. (登録日: 2016-11-29, 公開日: 2017-01-11, 最終更新日: 2024-01-17)

主引用文献

Desmet, J.,Verstraete, K.,Bloch, Y.,Lorent, E.,Wen, Y.,Devreese, B.,Vandenbroucke, K.,Loverix, S.,Hettmann, T.,Deroo, S.,Somers, K.,Henderikx, P.,Lasters, I.,Savvides, S.N.
Structural Basis Of Il-23 Antagonism By An Alphabody Protein Scaffold.
Nat Commun, 5:5237-, 2014

PubMed Abstract: Protein scaffolds can provide a promising alternative to antibodies for various biomedical and biotechnological applications, including therapeutics. Here we describe the design and development of the Alphabody, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold. We report affinity-matured Alphabodies with favourable physicochemical properties that can specifically neutralize human interleukin (IL)-23, a pivotal therapeutic target in autoimmune inflammatory diseases such as psoriasis and multiple sclerosis. The crystal structure of human IL-23 in complex with an affinity-matured Alphabody reveals how the variable interhelical groove of the scaffold uniquely targets a large epitope on the p19 subunit of IL-23 to harness fully the hydrophobic and hydrogen-bonding potential of tryptophan and tyrosine residues contributed by p19 and the Alphabody, respectively. Thus, Alphabodies are suitable for targeting protein-protein interfaces of therapeutic importance and can be tailored to interrogate desired design and binding-mode principles via efficient selection and affinity-maturation strategies.

PubMed: 25354530
DOI: 10.1038/NCOMMS6237

実験手法

X-RAY DIFFRACTION (1.74 Å)