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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

Isopeptide bonds and metal binding site. (A) The isopeptide bond between K978 on strand A and N1128 on strand F in the C2 domain is represented as a stick model in a 2Fo-Fc map, contoured at 0.90 e/Å3. It is stabilized by hydrogen bonding with the side chain of D1028 (dashed lines). (B) In the C2 domain a metal ion, modeled as a Ca2+ ion, is coordinated by D1029 and Y1030 on the strands C-D loop, V1084 and E1086 from the loop connecting helix DH1 with strand D″, and one water molecule. The figure is presented in stereo.
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f0015: Isopeptide bonds and metal binding site. (A) The isopeptide bond between K978 on strand A and N1128 on strand F in the C2 domain is represented as a stick model in a 2Fo-Fc map, contoured at 0.90 e/Å3. It is stabilized by hydrogen bonding with the side chain of D1028 (dashed lines). (B) In the C2 domain a metal ion, modeled as a Ca2+ ion, is coordinated by D1029 and Y1030 on the strands C-D loop, V1084 and E1086 from the loop connecting helix DH1 with strand D″, and one water molecule. The figure is presented in stereo.

Mentions: An isopeptide bond can be observed between K978 (on strand A) and N1128 (strand F) in domain C2, forming a covalent link between the S1 and S2 β-sheets of the β-sandwich motif. The interaction is completed by hydrogen bonding between the C000000000000000000000000000000000000111111111111000000000000111111111111000000000000000000000000000000000000O and NH isopeptide groups and the side chain of D1028 (Fig. 3A). Similarly K1155 (strand A) and N1286 (strand F) in domain C3 are connected by an isopeptide bond, stabilized by the side chain of D1201. The isopeptide bonds are surrounded by aromatic and hydrophobic residues. This may result in an increased pKa of the aspartic acid and decreased pKa of the lysine residue, facilitating nucleophilic attack on the Asn CG carbon by the deprotonated lysine amino group, finally yielding a covalent bond and the release of ammonium [19]. This type of self-generated stabilizing isopeptide bond has now been identified in a number of different pilin/adhesin proteins from Gram-positive bacteria [5,7,19–22]. Probably the extra structural stabilization inferred by the isopeptide bonds is essential for resistance against physical and chemical stress. Oral bacteria, for example, are constantly exposed to strong physical shear forces from salivary flow as well as tongue movement, and must remain firmly attached to host surfaces in order to persist and colonize.


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)

Isopeptide bonds and metal binding site. (A) The isopeptide bond between K978 on strand A and N1128 on strand F in the C2 domain is represented as a stick model in a 2Fo-Fc map, contoured at 0.90 e/Å3. It is stabilized by hydrogen bonding with the side chain of D1028 (dashed lines). (B) In the C2 domain a metal ion, modeled as a Ca2+ ion, is coordinated by D1029 and Y1030 on the strands C-D loop, V1084 and E1086 from the loop connecting helix DH1 with strand D″, and one water molecule. The figure is presented in stereo.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0015: Isopeptide bonds and metal binding site. (A) The isopeptide bond between K978 on strand A and N1128 on strand F in the C2 domain is represented as a stick model in a 2Fo-Fc map, contoured at 0.90 e/Å3. It is stabilized by hydrogen bonding with the side chain of D1028 (dashed lines). (B) In the C2 domain a metal ion, modeled as a Ca2+ ion, is coordinated by D1029 and Y1030 on the strands C-D loop, V1084 and E1086 from the loop connecting helix DH1 with strand D″, and one water molecule. The figure is presented in stereo.
Mentions: An isopeptide bond can be observed between K978 (on strand A) and N1128 (strand F) in domain C2, forming a covalent link between the S1 and S2 β-sheets of the β-sandwich motif. The interaction is completed by hydrogen bonding between the C000000000000000000000000000000000000111111111111000000000000111111111111000000000000000000000000000000000000O and NH isopeptide groups and the side chain of D1028 (Fig. 3A). Similarly K1155 (strand A) and N1286 (strand F) in domain C3 are connected by an isopeptide bond, stabilized by the side chain of D1201. The isopeptide bonds are surrounded by aromatic and hydrophobic residues. This may result in an increased pKa of the aspartic acid and decreased pKa of the lysine residue, facilitating nucleophilic attack on the Asn CG carbon by the deprotonated lysine amino group, finally yielding a covalent bond and the release of ammonium [19]. This type of self-generated stabilizing isopeptide bond has now been identified in a number of different pilin/adhesin proteins from Gram-positive bacteria [5,7,19–22]. Probably the extra structural stabilization inferred by the isopeptide bonds is essential for resistance against physical and chemical stress. Oral bacteria, for example, are constantly exposed to strong physical shear forces from salivary flow as well as tongue movement, and must remain firmly attached to host surfaces in order to persist and colonize.

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