7QUV

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

Summary for 7QUV

• Entry DOI: 10.2210/pdb7quv/pdb
• Descriptor: Protein S100-A9, 1,2-ETHANEDIOL, 4-methanoyl-2-(6-oxidanyl-3-oxidanylidene-4~{H}-xanthen-9-yl)benzoic acid, ... (13 entities in total)
• Functional Keywords: metal binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 28160.63

Authors

Diaz-Perlas, C.,Heinis, C.,Pojer, F.,Lau, K. (deposition date: 2022-01-19, release date: 2023-02-01, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)