Limits...
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

Overall topology of AspA-C2–3. (A) Ribbon diagram of AspA-C2–3 presented in stereo. The C2 domain (residues 971–1150) is depicted in blue while the C3 domain (1151–1306) is depicted in yellow. A bound calcium ion is shown as a grey sphere. (B) Topology diagram of AspA-C2–3 where α-helices are represented as rectangles, β-strands as arrows and loops as lines. The isopeptide bonds between K987 and N1128 and between K1155 and N1286 are marked as red lines. (C) Electrostatic surface potential rendering of AspA-C2–3 colored from −0.5 V (red) to 0.5 V (blue). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4048849&req=5

f0010: Overall topology of AspA-C2–3. (A) Ribbon diagram of AspA-C2–3 presented in stereo. The C2 domain (residues 971–1150) is depicted in blue while the C3 domain (1151–1306) is depicted in yellow. A bound calcium ion is shown as a grey sphere. (B) Topology diagram of AspA-C2–3 where α-helices are represented as rectangles, β-strands as arrows and loops as lines. The isopeptide bonds between K987 and N1128 and between K1155 and N1286 are marked as red lines. (C) Electrostatic surface potential rendering of AspA-C2–3 colored from −0.5 V (red) to 0.5 V (blue). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Mentions: The overall topology of the AspA-C2–3 structure is presented in Fig. 2, and is comprised of two distinct domains, referred to as the C2- and C3-domains (residues 971–1149 and 1150–1306 respectively). Together these two domains form an elongated structure, approximately 95 Å long and 35 Å wide. Each domain adopts the DEv-IgG fold [18], which similarly to the classical IgG folds is comprised of two major antiparallel β-sheets, designated ABED and CFG. The ABED sheet is formed by the A, B, E and D strands while the CFG sheet is correspondingly formed by strands C, F and G. The main variation from the classical IgG folds, including additional helices and strands, is found between the D and E strands. For the C2-domain, there are two additional strands on the CFG sheet, designated D′ and D″ as well as two α-helices, DH1 and DH2, located respectively on the loop region between strands D′ and D″ and between strands D″ and E. In addition an α-helix (BH1) is located in the loop region between strands B and C. The central DEv-IgG motif of the C3-domain is in a similar manner formed from the four stranded ABED and three stranded CFG main β-sheets. Two additional strands (D″′ and D″″) extend the CFG sheet into a five stranded sheet. As for the C2-domain, sheets ABED and CFG are interconnected by several cross-connecting loops and one α-helix (DH1) between strand D″″ of the CFG sheet and strand E of the ABED sheet. The C2- and C3-domain are connected by a linker extending from strand G in the C2-domain to strand A in the C3-domain. Additionally, in the interface region between the two domains, the side chains of D982 and N996 in the C2-domain are involved in hydrogen bonding with the side chains of R1264 and N1295 in the C3 domain. Main chain hydrogen bonding can also be observed between S992 in C2 and N1189/G1191 in C3, furthermore stabilizing the interaction between the domains. Finally the main chain atoms of the interface region exhibit low temperature factors, in the range similar to those for main chain atoms of the central DEv-IgG folds, suggesting that the domains are fixed in position and that the structure is rigid. The C2 domain contains one bound metal ion, modeled as Ca2+, and both the C2- and C3-domains are stabilized by conserved isopeptide bonds, which connect the β-sheets of the central DEv-IgG motifs. An electrostatic surface potential rendering shows that positively and negatively charged residues are heterogeneously distributed across the protein surface (Fig. 2C).


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)

Overall topology of AspA-C2–3. (A) Ribbon diagram of AspA-C2–3 presented in stereo. The C2 domain (residues 971–1150) is depicted in blue while the C3 domain (1151–1306) is depicted in yellow. A bound calcium ion is shown as a grey sphere. (B) Topology diagram of AspA-C2–3 where α-helices are represented as rectangles, β-strands as arrows and loops as lines. The isopeptide bonds between K987 and N1128 and between K1155 and N1286 are marked as red lines. (C) Electrostatic surface potential rendering of AspA-C2–3 colored from −0.5 V (red) to 0.5 V (blue). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0010: Overall topology of AspA-C2–3. (A) Ribbon diagram of AspA-C2–3 presented in stereo. The C2 domain (residues 971–1150) is depicted in blue while the C3 domain (1151–1306) is depicted in yellow. A bound calcium ion is shown as a grey sphere. (B) Topology diagram of AspA-C2–3 where α-helices are represented as rectangles, β-strands as arrows and loops as lines. The isopeptide bonds between K987 and N1128 and between K1155 and N1286 are marked as red lines. (C) Electrostatic surface potential rendering of AspA-C2–3 colored from −0.5 V (red) to 0.5 V (blue). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Mentions: The overall topology of the AspA-C2–3 structure is presented in Fig. 2, and is comprised of two distinct domains, referred to as the C2- and C3-domains (residues 971–1149 and 1150–1306 respectively). Together these two domains form an elongated structure, approximately 95 Å long and 35 Å wide. Each domain adopts the DEv-IgG fold [18], which similarly to the classical IgG folds is comprised of two major antiparallel β-sheets, designated ABED and CFG. The ABED sheet is formed by the A, B, E and D strands while the CFG sheet is correspondingly formed by strands C, F and G. The main variation from the classical IgG folds, including additional helices and strands, is found between the D and E strands. For the C2-domain, there are two additional strands on the CFG sheet, designated D′ and D″ as well as two α-helices, DH1 and DH2, located respectively on the loop region between strands D′ and D″ and between strands D″ and E. In addition an α-helix (BH1) is located in the loop region between strands B and C. The central DEv-IgG motif of the C3-domain is in a similar manner formed from the four stranded ABED and three stranded CFG main β-sheets. Two additional strands (D″′ and D″″) extend the CFG sheet into a five stranded sheet. As for the C2-domain, sheets ABED and CFG are interconnected by several cross-connecting loops and one α-helix (DH1) between strand D″″ of the CFG sheet and strand E of the ABED sheet. The C2- and C3-domain are connected by a linker extending from strand G in the C2-domain to strand A in the C3-domain. Additionally, in the interface region between the two domains, the side chains of D982 and N996 in the C2-domain are involved in hydrogen bonding with the side chains of R1264 and N1295 in the C3 domain. Main chain hydrogen bonding can also be observed between S992 in C2 and N1189/G1191 in C3, furthermore stabilizing the interaction between the domains. Finally the main chain atoms of the interface region exhibit low temperature factors, in the range similar to those for main chain atoms of the central DEv-IgG folds, suggesting that the domains are fixed in position and that the structure is rigid. The C2 domain contains one bound metal ion, modeled as Ca2+, and both the C2- and C3-domains are stabilized by conserved isopeptide bonds, which connect the β-sheets of the central DEv-IgG motifs. An electrostatic surface potential rendering shows that positively and negatively charged residues are heterogeneously distributed across the protein surface (Fig. 2C).

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