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Structure of the C-terminal domain of AspA (antigen I/II-family) protein from Streptococcus pyogenes.

Hall M, Nylander S, Jenkinson HF, Persson K - FEBS Open Bio (2014)

Bottom Line: The antigen I/II family proteins are cell wall anchored adhesin proteins found on the surfaces of most oral streptococci and are involved in host colonization and biofilm formation.Despite relatively low sequence identity, interestingly, the overall structure shares high similarity to the C2-3-domains of antigen I/II proteins from Streptococcus gordonii and Streptococcus mutans, although certain parts of the structure exhibit distinct features.In summary this work constitutes the first step in the full structure determination of the AspA protein from S. pyogenes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.

ABSTRACT
The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in humans, including moderate infections such as pharyngitis (strep throat) as well as life threatening conditions such as necrotizing fasciitis and puerperal fever. The antigen I/II family proteins are cell wall anchored adhesin proteins found on the surfaces of most oral streptococci and are involved in host colonization and biofilm formation. In the present study we have determined the crystal structure of the C2-3-domain of the antigen I/II type protein AspA from S. pyogenes M type 28. The structure was solved to 1.8 Å resolution and shows that the C2-3-domain is comprised of two structurally similar DEv-IgG motifs, designated C2 and C3, both containing a stabilizing covalent isopeptide bond. Furthermore a metal binding site is identified, containing a bound calcium ion. Despite relatively low sequence identity, interestingly, the overall structure shares high similarity to the C2-3-domains of antigen I/II proteins from Streptococcus gordonii and Streptococcus mutans, although certain parts of the structure exhibit distinct features. In summary this work constitutes the first step in the full structure determination of the AspA protein from S. pyogenes.

No MeSH data available.


Related in: MedlinePlus

Domain organization of S. pyogenes AspA and sequence alignment of the C2–3 domains of AspA, SpaP and SspB. (A) The primary sequence of AspA begins with a signal peptide (SP), followed in sequence by a small N-terminal domain (N), an alanine rich repeat region (A), a variable domain (V), a proline rich repeat region (P), a C-terminal region (C), and finally a cell wall anchor segment (CW) containing an LPxTG-motif for sortase mediated cell wall attachment. (B) Sequence alignment of the AspA (Uniprot id. Q48S75), SpaP (P23404) and SspB (P16952) C2–3 domains. Secondary structure elements from the structure of AspA-C2–3 are marked above the alignment.
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f0005: Domain organization of S. pyogenes AspA and sequence alignment of the C2–3 domains of AspA, SpaP and SspB. (A) The primary sequence of AspA begins with a signal peptide (SP), followed in sequence by a small N-terminal domain (N), an alanine rich repeat region (A), a variable domain (V), a proline rich repeat region (P), a C-terminal region (C), and finally a cell wall anchor segment (CW) containing an LPxTG-motif for sortase mediated cell wall attachment. (B) Sequence alignment of the AspA (Uniprot id. Q48S75), SpaP (P23404) and SspB (P16952) C2–3 domains. Secondary structure elements from the structure of AspA-C2–3 are marked above the alignment.

Mentions: In the genome of S. pyogenes serotype M28, a single AgI/II type protein is encoded by the aspA gene. The gene product, AspA, is comprised of 1352 amino acids and is expected to exhibit the typical AgI/II protein domain architecture (Fig. 1A). Similarly as observed for SpaP from S. mutans and SspA and SspB from S. gordonii, the AspA protein contains three repeat regions in the A-domain, three repeat regions in the P-domain, and also the C-domain can be divided into three subdomains. Although the general structural characteristics are predicted to be similar, the overall sequence identity between AspA and SpaP is only 27% (and 28% between AspA and SspA/B). A sequence alignment of the C2–3 regions of AspA, SpaP and SspB is shown in Fig. 1B. Especially the AspA V-domain, which shares only 8% sequence identity with the V-domain of SpaP, appears to be functionally distinct from those of SpaP, SspA and SspB. Interestingly, the V-domain shares high sequence similarity with the V-domain of the AgI/II protein BspD from Streptococcus agalactiae, and they both contain conserved histidine–aspartic acid clusters, typically associated with divalent metal binding sites [4]. In agreement with this observation it was recently shown that the V-domain of AspA could indeed bind divalent metal ions, specifically Zn2+ ions [10]. However, the functional significance of the Zn2+ binding remains unknown. In the same study it was also concluded that AspA can bind immobilized salivary agglutinin gp-340 and that deletion of the aspA gene abolished the abilities of two different M28 strains of S. pyogenes to form biofilms on saliva coated surfaces [10].


Structure of the C-terminal domain of AspA (antigen I/II-family) protein from Streptococcus pyogenes.

Hall M, Nylander S, Jenkinson HF, Persson K - FEBS Open Bio (2014)

Domain organization of S. pyogenes AspA and sequence alignment of the C2–3 domains of AspA, SpaP and SspB. (A) The primary sequence of AspA begins with a signal peptide (SP), followed in sequence by a small N-terminal domain (N), an alanine rich repeat region (A), a variable domain (V), a proline rich repeat region (P), a C-terminal region (C), and finally a cell wall anchor segment (CW) containing an LPxTG-motif for sortase mediated cell wall attachment. (B) Sequence alignment of the AspA (Uniprot id. Q48S75), SpaP (P23404) and SspB (P16952) C2–3 domains. Secondary structure elements from the structure of AspA-C2–3 are marked above the alignment.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048849&req=5

f0005: Domain organization of S. pyogenes AspA and sequence alignment of the C2–3 domains of AspA, SpaP and SspB. (A) The primary sequence of AspA begins with a signal peptide (SP), followed in sequence by a small N-terminal domain (N), an alanine rich repeat region (A), a variable domain (V), a proline rich repeat region (P), a C-terminal region (C), and finally a cell wall anchor segment (CW) containing an LPxTG-motif for sortase mediated cell wall attachment. (B) Sequence alignment of the AspA (Uniprot id. Q48S75), SpaP (P23404) and SspB (P16952) C2–3 domains. Secondary structure elements from the structure of AspA-C2–3 are marked above the alignment.
Mentions: In the genome of S. pyogenes serotype M28, a single AgI/II type protein is encoded by the aspA gene. The gene product, AspA, is comprised of 1352 amino acids and is expected to exhibit the typical AgI/II protein domain architecture (Fig. 1A). Similarly as observed for SpaP from S. mutans and SspA and SspB from S. gordonii, the AspA protein contains three repeat regions in the A-domain, three repeat regions in the P-domain, and also the C-domain can be divided into three subdomains. Although the general structural characteristics are predicted to be similar, the overall sequence identity between AspA and SpaP is only 27% (and 28% between AspA and SspA/B). A sequence alignment of the C2–3 regions of AspA, SpaP and SspB is shown in Fig. 1B. Especially the AspA V-domain, which shares only 8% sequence identity with the V-domain of SpaP, appears to be functionally distinct from those of SpaP, SspA and SspB. Interestingly, the V-domain shares high sequence similarity with the V-domain of the AgI/II protein BspD from Streptococcus agalactiae, and they both contain conserved histidine–aspartic acid clusters, typically associated with divalent metal binding sites [4]. In agreement with this observation it was recently shown that the V-domain of AspA could indeed bind divalent metal ions, specifically Zn2+ ions [10]. However, the functional significance of the Zn2+ binding remains unknown. In the same study it was also concluded that AspA can bind immobilized salivary agglutinin gp-340 and that deletion of the aspA gene abolished the abilities of two different M28 strains of S. pyogenes to form biofilms on saliva coated surfaces [10].

Bottom Line: The antigen I/II family proteins are cell wall anchored adhesin proteins found on the surfaces of most oral streptococci and are involved in host colonization and biofilm formation.Despite relatively low sequence identity, interestingly, the overall structure shares high similarity to the C2-3-domains of antigen I/II proteins from Streptococcus gordonii and Streptococcus mutans, although certain parts of the structure exhibit distinct features.In summary this work constitutes the first step in the full structure determination of the AspA protein from S. pyogenes.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.

ABSTRACT
The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in humans, including moderate infections such as pharyngitis (strep throat) as well as life threatening conditions such as necrotizing fasciitis and puerperal fever. The antigen I/II family proteins are cell wall anchored adhesin proteins found on the surfaces of most oral streptococci and are involved in host colonization and biofilm formation. In the present study we have determined the crystal structure of the C2-3-domain of the antigen I/II type protein AspA from S. pyogenes M type 28. The structure was solved to 1.8 Å resolution and shows that the C2-3-domain is comprised of two structurally similar DEv-IgG motifs, designated C2 and C3, both containing a stabilizing covalent isopeptide bond. Furthermore a metal binding site is identified, containing a bound calcium ion. Despite relatively low sequence identity, interestingly, the overall structure shares high similarity to the C2-3-domains of antigen I/II proteins from Streptococcus gordonii and Streptococcus mutans, although certain parts of the structure exhibit distinct features. In summary this work constitutes the first step in the full structure determination of the AspA protein from S. pyogenes.

No MeSH data available.


Related in: MedlinePlus