7QUV

Crystal structure of human Calprotectin (S100A8/S100A9) in complex with Peptide 3

7QUV の概要

• エントリーDOI: 10.2210/pdb7quv/pdb
• 分子名称: Protein S100-A9, 1,2-ETHANEDIOL, 4-methanoyl-2-(6-oxidanyl-3-oxidanylidene-4~{H}-xanthen-9-yl)benzoic acid, ... (13 entities in total)
• 機能のキーワード: metal binding protein
• 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: 28160.63

構造登録者

Diaz-Perlas, C.,Heinis, C.,Pojer, F.,Lau, K. (登録日: 2022-01-19, 公開日: 2023-02-01, 最終更新日: 2024-02-07)

主引用文献

Diaz-Perlas, C.,Ricken, B.,Farrera-Soler, L.,Guschin, D.,Pojer, F.,Lau, K.,Gerhold, C.B.,Heinis, C.
High-affinity peptides developed against calprotectin and their application as synthetic ligands in diagnostic assays.
Nat Commun, 14:2774-2774, 2023

PubMed Abstract: Common inflammatory disorders such as ulcerative colitis and Crohn's disease are non-invasively diagnosed or monitored by the biomarker calprotectin. However, current quantitative tests for calprotectin are antibody-based and vary depending on the type of antibody and assay used. Additionally, the binding epitopes of applied antibodies are not characterized by structures and for most antibodies it is unclear if they detect calprotectin dimer, tetramer, or both. Herein, we develop calprotectin ligands based on peptides, that offer advantages such as homogenous chemical composition, heat-stability, site-directed immobilization, and chemical synthesis at high purity and at low cost. By screening a 100-billion peptide phage display library against calprotectin, we identified a high-affinity peptide (K = 26 ± 3 nM) that binds to a large surface region (951 Å) as shown by X-ray structure analysis. The peptide uniquely binds the calprotectin tetramer, which enabled robust and sensitive quantification of a defined species of calprotectin by ELISA and lateral flow assays in patient samples, and thus offers an ideal affinity reagent for next-generation inflammatory disease diagnostic assays.

PubMed: 37198182
DOI: 10.1038/s41467-023-38075-7

実験手法

X-RAY DIFFRACTION (1.85 Å)