Polymer Adhesin Domains in Gram-Positive Cell Surface Proteins

Abstract

Surface proteins in Gram-positive bacteria are often involved in biofilm formation, host-cell interactions, and surface attachment. Here we review a protein module found in surface proteins that are often encoded on various mobile genetic elements like conjugative plasmids. This module binds to different types of polymers like DNA, lipoteichoic acid and glucans, and is here termed polymer adhesin domain. We analyze all proteins that contain a polymer adhesin domain and classify the proteins into distinct classes based on phylogenetic and protein domain analysis. Protein function and ligand binding show class specificity, information that will be useful in determining the function of the large number of so far uncharacterized proteins containing a polymer adhesin domain.

Keywords: Gram-positive; adhesin; binding; biofilm; conjugation.

FIGURE 1

(A) Phylogenetic tree of a representative subset (<90% identity) of the polymer adhesin domain sequences as annotated in InterPro (Mitchell et al., 2019). Alignments done by ClustalO were used to calculate the phylogenetic relationships with PhyML (Dereeper et al., 2008) using 100 bootstraps. Visualization was done with iTol and brances with a bootstrap lower than 0.5 were collapsed. Each node is annotated with its respective UNIPROT accession code (in two instances refseq) and organism name. Clades are color coded, and nodes with associated literature are marked with a star. (B) Pruned tree highlighting the 21 reviewed protein entries, using the same class color coding as in panel (A). Here the additional annotations include common protein name, and domain architecture as annotated by InterPro (Mitchell et al., 2019).

FIGURE 2

All available protein structures of unique proteins from three different classes of polymer adhesin containing proteins. Here drawn as cartoon representations, colored blue to red from the N-terminus and viewed from the same angle, the similarities in overall fold is seen, as well as their conserved cation binding site (red sphere) situated in the middle of the central ridge.

FIGURE 3

Same proteins as in Figure 2 but using electrostatic surface representations and in the case of PrgB its eDNA ligand is shown binding to the positively charged surface.

FIGURE 4

Planktonic cells utilize their polymer adhesin domain to attach to various surfaces by binding various molecules such as (i) coiled-coil proteins in extracellular matrix, (ii) polysaccharides, and (iii) negatively charged polymers such as eDNA and lipoteichoic acid. The attachment to these further drives the formation of cellular biofilms. Enzymatic cleavage of the polymer adhesin domain might aid in the dispersal of cells from mature biofilms. Created with BioRender.