Most cited article - PubMed ID 38750795
Evolutionary insights into sequence modifications governing chitin recognition and chitinase inactivity in YKL-40 (HC-gp39, CHI3L1)
YKL-40 is structurally similar to chitotriosidase (CHIT1), an active chitinase, but it lacks chitin-degrading activity while retaining chitin-binding capability. Elevated YKL-40 levels are associated with inflammatory diseases and cancers, making it a valuable biomarker. We previously reported that the W69T substitution in YKL-40 significantly reduces its chitin-binding affinity, identifying W69 as a crucial binding site. In this study, we establish a novel chitin-binding affinity evaluation method using a three-step buffer system to assess the binding strength and specificity of chitin-binding proteins and apply it to characterize YKL-40's binding mechanism. Our findings confirm that YKL-40, through its key residue W69, exhibits highly specific and robust affinity to chitin. Unlike CHIT1, which has both a catalytic domain (CatD) and a chitin-binding domain (CBD) that allow for diverse binding and degradation activities, YKL-40 lacks a CBD and is specialized for specific chitin recognition without degrading it. Comparative analysis with YKL-39, which does not contain a corresponding W69 residue, highlights the unique role of this residue in YKL-40's chitin-binding activity that is potentially linked to immune and inflammatory responses. Our evaluation method clarifies YKL-40's binding properties and provides a versatile approach applicable to other chitin-binding proteins.
- Keywords
- W69 residue, YKL-39, YKL-40, catalytic domain (CatD), chitin, chitin-binding activity, chitin-binding affinity assay, chitin-binding domain (CBD), chitinase-like proteins (CLPs), chitotriosidase (CHIT1),
- MeSH
- Chitin * metabolism chemistry MeSH
- Hexosaminidases * metabolism chemistry MeSH
- Humans MeSH
- Chitinase-3-Like Protein 1 * metabolism chemistry genetics MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- CHI3L1 protein, human MeSH Browser
- Chitin * MeSH
- chitotriosidase MeSH Browser
- Hexosaminidases * MeSH
- Chitinase-3-Like Protein 1 * MeSH
