Collagen Binding Proteins of Gram-Positive Pathogens

Abstract

Collagens are the primary structural components of mammalian extracellular matrices. In addition, collagens regulate tissue development, regeneration and host defense through interaction with specific cellular receptors. Their unique triple helix structure, which requires a glycine residue every third amino acid, is the defining structural feature of collagens. There are 28 genetically distinct collagens in humans. In addition, several other unrelated human proteins contain a collagen domain. Gram-positive bacteria of the genera Staphylococcus, Streptococcus, Enterococcus, and Bacillus express cell surface proteins that bind to collagen. These proteins of Gram-positive pathogens are modular proteins that can be classified into different structural families. This review will focus on the different structural families of collagen binding proteins of Gram-positive pathogen. We will describe how these proteins interact with the triple helix in collagens and other host proteins containing a collagenous domain and discuss how these interactions can contribute to the pathogenic processes.

Keywords: Gram-positive bacteria; collagen; collagen binding proteins; collagen-like proteins; surface proteins.

FIGURE 1

Cartoon representation showing domain organization of collagen binding proteins. Each protein has a signal peptide (SS) at the N-terminus. With the exception of Slr, each protein has a LPXTG motif, and a cell wall-spanning transmembrane region (black). Confirmed and putative collagen-binding domains in the proteins are colored in blue. Where two domains are involved in collagen binding, the first domain is light blue and the second domain is colored darker blue. Proline-glycine rich region of M6 protein is shown in salmon color.

FIGURE 2

Collagen hug model. The N1N2 domains of CNA in both apo-form [PDB code: 2F68 (Zong et al., 2005)] and with collagen peptide [PDB code: 2F6A (Zong et al., 2005)] are shown. N2 and N1 domains are shown in dark blue and light teal color, respectively. CNA N1N2 domains are connected together by a linker shown in red. Collagen triple helix is shown in green. C-terminal extension of the N2 domain that forms a latch is shown as dark blue β-strand in N1 domain.

FIGURE 3

Tip pilus protein RrgA. (A) Tip pilus protein RrgA of S. pneumoniae [PDB code: 2WW8 (Izore et al., 2010)] contains a D3 domain with vWA fold (shown in teal), D1 (shown in dark gray), and D4 domains (shown in light brown) with an IgG-rev fold, and a D2 domain (shown in light gray) with a Dev-IgG fold. The collagen-binding D3 domain is positioned at the tip and contains two inserted arms in the D3 domain. First inserted arm is shown in yellow and second inserted arm is shown in red. (B) Figure shows two predicted collagen binding sites on the surface of D3 domain of RrgA. D3 domain, first inserted arm and second inserted arm are shown in light teal, yellow and red, respectively. The U-shaped cradle on the top of D3 domain is formed by two inserted arms. Magnesium ion present in MIDAS motif is shown as white sphere in the trench and residues interacting with magnesium ion (S234, S236, and D387) are shown in dark blue.

FIGURE 4

N1N2 domains of Sgo0707. (A) N1 and N2 domains of Sgo0707 from S. gordonii [PDB code: 4IGB (Nylander et al., 2013)] are shown in light teal and dark blue, respectively. (B) Figure shows predicted collagen binding site present in the N1 domain. (C) Figure shows second predicted collagen binding site formed the loops of the N1 domain and a β-sheet of the N2 domain. This site forms a concave surface where collagen can dock.