Domain structure and cross-linking in a giant adhesin from the Mobiluncus mulieris bacterium

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Adhesins are bacterial cell-surface proteins crucial for colonization.
• Gram-positive bacteria often utilize intramolecular cross-links in adhesins.
• Mobiluncus mulieris is a pathogen associated with bacterial vaginosis.

Purpose of the Study:

• To investigate the prevalence and structure of cross-links in bacterial adhesins.
• To characterize a large putative adhesin from Mobiluncus mulieris.
• To determine the structural family and potential function of this adhesin.

Main Methods:

• X-ray crystallography and mass spectrometry were used to analyze specific protein domains.
• AlphaFold structure prediction was employed for the remaining protein sequence.
• Bioinformatic analysis was performed to identify protein families and domains.

Main Results:

• A 7651-residue adhesin from Mobiluncus mulieris was identified.
• The adhesin belongs to the thioester, isopeptide, and ester-bond-containing (TIE) protein family.
• It features an N-terminal thioester adhesion domain and 51 immunoglobulin-like domains with covalent cross-links.

Conclusions:

• The large size and complex cross-linking of the M. mulieris adhesin suggest significant energetic investment by the bacterium.
• This unique adhesin likely plays a critical role in the pathogenicity and/or persistence of Mobiluncus mulieris.
• Further research into TIE proteins may reveal novel mechanisms of bacterial adhesion and virulence.