# Differential Binding of ΔFN3 Proteins of Bifidobacterium longum GT15 and Bifidobacterium bifidum 791 to Cytokines Determined by Surface Plasmon Resonance and De Novo Molecular Modeling

## TL;DR

This study explores how proteins from two types of bifidobacteria bind to immune-related molecules, revealing structural differences that may influence immune responses.

## Contribution

The study presents de novo structural models of ∆FN3 proteins and identifies new regions for cytokine binding.

## Key findings

- Recombinant ∆FN3 fragments from B. longum and B. bifidum interact differently with cytokines like TNF-α, IL-6, IL-8, and IL-10.
- De novo modeling revealed tentative structural regions responsible for differential cytokine binding.
- Combined treatment with ∆FN3 and TNF-α increased TNF-α mRNA in human monocytic cells.

## Abstract

Bifidobacteria, a genus of obligate anaerobes, comprise a major component of the intestinal microbiota. Importantly, bifidobacteria participate in immune reactions. These bacteria carry a species-specific operon in which the fn3 gene encodes a multifunctional protein FN3 that mediates bacterial adhesion to the intestinal epithelium and is capable of binding individual cytokines. Bioinformatics and biochemical approaches were used to study the possible interaction of recombinant ∆FN3 fragments of B. longum and B. bifidum strains with cytokines TNF-α, IL-6, IL-8, and IL-10. De novo molecular modeling generated, for the first time, the structural models of species-derived ∆FN3 proteins and revealed new tentative regions for differential cytokine binding. Combined treatment with ∆FN3 and TNF-α induced TNF-α mRNA abundance in the human monocytic cell line. Altogether, these findings provide structural evidence for the regulation of immune reactions by microbiota-derived proteins.