Human ZG16p recognizes pathogenic fungi through non-self polyvalent mannose in the digestive system

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Human zymogen granule protein 16 (ZG16p) possesses a Jacalin-like lectin domain with unknown glycan-binding properties.
• Lectins play crucial roles in biological recognition processes, including host-pathogen interactions.

Purpose of the Study:

• To elucidate the glycan-binding specificity of ZG16p.
• To investigate the biological function of ZG16p in the digestive system and its role in recognizing pathogenic fungi.

Main Methods:

• Glycoconjugate microarray screening to determine ZG16p binding specificity.
• Frontal affinity chromatography for quantitative analysis of binding affinities.
• Site-directed mutagenesis to identify key amino acids for mannose binding.
• Immunohistochemical staining to localize ZG16p expression in tissues.
• Fungal recognition assays using pathogenic Candida and Malassezia species.

Main Results:

• ZG16p selectively binds to α- and β-linked mannose probes.
• Dissociation constants for ZG16p binding to polyvalent mannose and yeast mannan were determined to be 1.3 µM and 1.7 µM, respectively.
• Mutation of Asp151 abolished mannose-binding activity, confirming its role in sugar recognition.
• ZG16p is localized in mucus-secreting cells of the digestive system, including salivary glands, pancreas, and intestine.
• ZG16p recognizes pathogenic Candida and Malassezia species in a mannose-dependent manner.

Conclusions:

• ZG16p is a novel mannose-specific Jacalin-related lectin (JRL).
• ZG16p recognizes pathogenic fungi via non-self polyvalent mannose in the digestive tract.
• ZG16p likely plays a role in innate immunity against fungal infections in the digestive system.