# Characterization of YKL-40 Binding to Extracellular Matrix Glycosaminoglycans

## TL;DR

This study identifies new binding partners for the protein YKL-40, revealing its interactions with dermatan sulfate and hyaluronan in addition to heparin.

## Contribution

The study discovers new glycosaminoglycan ligands for YKL-40 and identifies a shared binding site for heparin and dermatan sulfate.

## Key findings

- YKL-40 binds to dermatan sulfate and hyaluronan with detectable affinity.
- Heparin shows the strongest binding affinity to YKL-40, followed by dermatan sulfate and hyaluronan.
- Molecular docking suggests heparin and dermatan sulfate bind to the same site on YKL-40.

## Abstract

YKL-40 is a chitinase-like glycoprotein implicated in various pathological processes, yet its glycosaminoglycan (GAG) binding profile beyond heparin has not been examined. In this study, we performed a Microscale Thermophoresis (MST) analysis on the heparin-binding glycoprotein YKL-40 using low molecular weight GAG oligosaccharides. We identified two new GAG ligands, dermatan sulfate (DS) and hyaluronan (HA), while chondroitin sulfate (CS) showed no detectable binding affinity. The results show that heparin is bound with the strongest affinity, followed by DS and HA. To further investigate these differences, molecular docking was used to evaluate possible binding modes. Molecular docking results indicated that both heparin and DS interacted with the same site on YKL-40, the heparin-binding site at residues 143–149, suggesting a multifunctional binding region that may act as a competitive switch or integration hub for spatially regulated signaling. Together, these findings expand the known ligand profile of YKL-40 and offer new insights into its ECM-context-dependent roles, with implications for targeting YKL-40 in diseases involving chronic inflammation, fibrosis, and cancer progression.