Sticking to the Subject: Multifunctionality in Microbial Adhesins

Abstract

Bacterial and fungal adhesins mediate microbial aggregation, biofilm formation, and adhesion to host. We divide these proteins into two major classes: professional adhesins and moonlighting adhesins that have a non-adhesive activity that is evolutionarily conserved. A fundamental difference between the two classes is the dissociation rate. Whereas moonlighters, including cytoplasmic enzymes and chaperones, can bind with high affinity, they usually dissociate quickly. Professional adhesins often have unusually long dissociation rates: minutes or hours. Each adhesin has at least three activities: cell surface association, binding to a ligand or adhesive partner protein, and as a microbial surface pattern for host recognition. We briefly discuss Bacillus subtilis TasA, pilin adhesins, gram positive MSCRAMMs, and yeast mating adhesins, lectins and flocculins, and Candida Awp and Als families. For these professional adhesins, multiple activities include binding to diverse ligands and binding partners, assembly into molecular complexes, maintenance of cell wall integrity, signaling for cellular differentiation in biofilms and in mating, surface amyloid formation, and anchorage of moonlighting adhesins. We summarize the structural features that lead to these diverse activities. We conclude that adhesins resemble other proteins with multiple activities, but they have unique structural features to facilitate multifunctionality.

Lymphostatin: Structure of a large multi-functional virulence factor

“…The N-terminal ß-sandwich (S1) was the largest, containing 42 strands (residues 2060-2629) while S2-S4 had only 7-10 strands. Such ß-sandwiches are typical for bacterial translocation and pore forming systems, as well as receptor binding and adhesion domains [12,27,28,29]. The relative arrangement of S2-S3 changed between conformation I and II.…”

Moonlighting Proteins: Diverse Functions Found in Fungi

“…For clarity, we are grouping the proteins into four groups based on whether the additional function plays a role in 1. affecting transcription, DNA metabolism, or DNA maintenance; 2. affecting translation or RNA metabolism; 3. affecting another protein's function; or 4. interacting with host cells or proteins (Figure 1). Additional fungal moonlighting proteins are described in other papers in this collection, including surface proteases that have additional functions such as acting as adhesins to host proteins [72]; cell surface adhesins with additional functions [73]; and a protein with different functions in multiple protein complexes, Hal3 [38].…”