Crystal structure of a mucus-binding protein repeat reveals an unexpected functional immunoglobulin binding activity

Area of Science:

• Microbiology
• Structural Biology
• Immunology

Background:

• Lactobacillus reuteri mucus-binding protein (MUB) is a large, modular adhesin crucial for bacterial interaction with host mucus and gut colonization.
• Understanding MUB's structure is key to characterizing this important class of bacterial adhesins.

Purpose of the Study:

• To determine the crystal structure of a type 2 Mub repeat (Mub2) from Lactobacillus reuteri.
• To investigate the structural relationship of Mub repeats to other known protein structures.
• To explore the potential immunoglobulin-binding capabilities of Mub repeats.

Main Methods:

• X-ray crystallography was used to determine the 1.8-Å resolution structure of a type 2 Mub repeat.
• Structural comparisons were made with known protein databases.
• In vitro assays were performed to assess the interaction of Mub repeats with mammalian immunoglobulins (Igs).

Main Results:

• The crystal structure revealed that a type 2 Mub repeat consists of two structurally related domains.
• These domains exhibit significant structural similarity to the repeat unit of Protein L (PpL) from Peptostreptococcus magnus.
• Mub repeats demonstrated in vitro binding to a wide range of mammalian Igs, including secretory IgA.

Conclusions:

• The structural similarity of Mub repeats to PpL suggests a non-immune Fab-dependent binding mechanism.
• The newly identified immunoglobulin-binding activity of MUB provides a potential mechanism for bacterial persistence in the gut.
• This finding supports models of broad-specificity, low-affinity antibody responses against commensal bacteria.