Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Immune tolerance can hinder responses to microbes displaying self-like antigens, such as blood group structures.
• Microbes can mimic human blood group antigens, evading immune detection.

Purpose of the Study:

• To investigate the binding and antimicrobial activity of galectin-4 (Gal-4) against microbes with blood group-like antigens.
• To elucidate the structural basis of Gal-4's function, particularly its dimerization and domain activity.

Main Methods:

• Utilized microarrays with ABO(H) glycans and various microbial strains to assess Gal-4 binding.
• Analyzed the dimerization properties and binding affinities of Gal-4's N-terminal (Gal-4N) and C-terminal (Gal-4C) domains.
• Compared the antimicrobial activity of Gal-4N, Gal-4C, and full-length Gal-4.

Main Results:

• Galectin-4 (Gal-4) binds to both mammalian and microbial antigens with blood group-like features.
• Gal-4 forms dimers, with the C-terminal domain (Gal-4C) exhibiting higher dimerization affinity and binding to ABO(H) antigens.
• Gal-4C demonstrated more potent antimicrobial activity than Gal-4N, even within the full-length protein.

Conclusions:

• Galectin-4 (Gal-4) functions as a dimer, primarily utilizing its C-terminal domain (Gal-4C) for antimicrobial activity.
• The C-terminal domain's dimerization and binding properties are crucial for Gal-4's innate immune function against molecular mimicry.
• These findings offer insights into Gal-4's mechanism against microbes displaying self-like antigens.