Structure of the C-terminal domain of the surface antigen SpaP from the caries pathogen<i>Streptococcus mutans</i>

Nylander, Åsa; Forsgren, Nina; Persson, Karina

doi:10.1107/s174430911004443x

Cited by 17 publications

(31 citation statements)

References 14 publications

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“…The C-terminal domain of BspA lacks a discrete C1 subdomain, proposed to enable the binding of carbohydrates or glycoproteins via the C1-C2 interface. Furthermore, the absence of bound metal ions, suggested in other AgI/II family polypeptide C-terminal domains to affect stability and adhesive properties (13)(14)(15)(16), may indicate altered binding behavior. Although it is not possible to discount metal binding capability entirely based on our crystallographic studies, variations in aa composition within the C2 and C3 metal-binding sites are consistent with loss of this function.…”

Section: Discussionmentioning

confidence: 99%

“…6A and comprise a pair of compact subdomains (residues 554 -725 and 726 -881 of full-length BspA) fused by a linker. The two subdomains are equivalent to those termed C2 and C3 in other AgI/II family polypeptides (13)(14)(15)(16). The absence of a C1 subdomain, a feature that is present in all other AgI/II family proteins characterized to date, accounts for the size disparity between BspA-C domain and other AgI/II family C domains.…”

Section: Distribution Of Agi/ii Polypeptides In Gbs-mentioning

confidence: 95%

“…Previously reported crystal structures of AgI/II family polypeptide C-terminal domains have identified the presence of bound metal ions, which have been suggested to play a role in enhancing stability and conferring adhesive properties (13)(14)(15)(16). By contrast, no bound metal ions are observed in the crystal structures of BspA-C G744D or BspA-C. BspA-C2 subdomain does possess a putative unoccupied metal-binding site, equivalently positioned to those reported in SpaP-C2, SspB-C2, and AspA-C2.…”

Section: Distribution Of Agi/ii Polypeptides In Gbs-mentioning

confidence: 99%

“…Crystal structures of the V regions of SpaP and SspB have revealed a common architecture consisting of a lectin-like fold with a putative binding cleft (11,12). The structure of the C-terminal subdomains C1, C2, and C3 has also been elucidated by x-ray crystallography and found to consist of ␤-sandwich domains stabilized by isopeptide bonds (13)(14)(15)(16).…”

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confidence: 99%

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Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

Rego

Heal

Pidwill

et al. 2016

Journal of Biological Chemistry

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Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans. Complementary crystallographic and biophysical characterization of BspA reveal a novel ␤-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections. Streptococcus agalactiae (group B Streptococcus (GBS)4 ) is a commensal of the gastrointestinal tract and part of the normal microbiota of the female rectovaginal tract, where it is carried asymptomatically by ϳ10 -40% of women of childbearing age (1). However, as an opportunistic pathogen, GBS is the leading cause of neonatal meningitis and sepsis in the developed world. The predominant route by which GBS is transmitted to infants is from the mother, either during birth or following breach of the placental barrier in utero. Antenatal GBS screening strategies are therefore commonly used to identify colonized women, who then receive antimicrobial prophylaxis. Nevertheless, GBS remains a major cause of morbidity and mortality in infants worldwide (2).Because maternal GBS colonization is the primary risk factor for vertical transmission of neonatal infection (3), there has been considerable focus on the mechanisms underlying GBS colonization of the female genitourinary (GU) tract. A number of putative colonization determinants have been identified, including the following: ␣C protein, mediating entry of GBS into cervical epithelial cells (4); pili, shown to contribute to vaginal attachment (5); and Srr-1, which binds keratin-4 (5) and fibrinogen (6) on the surface of vaginal epithelium. In addition, GBS expresses numerous extracellular matrix-binding proteins, including C5a peptidase (ScpB) and FbsA, which may promote attachment to mucosal tissues of the GU tract (7).Antigen I/II (AgI/II) family polypeptide adhesins are found widely across the Streptococcus genus and have been best characterized for those streptococci indigenous to the oral cavity (8). In silico analyses have recently revealed the presence of genes encoding AgI/II family polypeptides in GBS, which we have designated here group B Streptococcus surface proteins (Bsp). These proteins conform to a conserved primary structure consisting of seven distinct regions (Fig. 1). The N-terminal region comprises a signal (leader) peptide, an N-terminal domain, and an ...

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Section: Discussionmentioning

confidence: 99%

Section: Distribution Of Agi/ii Polypeptides In Gbs-mentioning

confidence: 95%

Section: Distribution Of Agi/ii Polypeptides In Gbs-mentioning

confidence: 99%

mentioning

confidence: 99%

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Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

Rego

Heal

Pidwill

et al. 2016

Journal of Biological Chemistry

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“…Although the functional structure comprising the N-terminal and central regions of S. mutans AgI/II has been well characterized (16), the complete and functional C-terminal region has not yet been described. A partial C-terminal structure of the S. mutans AgI/II (SpaP) (18) and a homologous fragment from the Streptococcus gordonii SspB were recently reported (19), where each structure had two IgG-like domains.…”

mentioning

confidence: 99%

Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

Larson

Rajashankar

Crowley

et al. 2011

Journal of Biological Chemistry

126

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The Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein that adheres to salivary components and extracellular matrix molecules. Here we report the 2.5 Å resolution crystal structure of the complete C-terminal region of AgI/ II. The C-terminal region is comprised of three major domains: C 1 , C 2 , and C 3 . Each domain adopts a DE-variant IgG fold, with two ␤-sheets whose A and F strands are linked through an intramolecular isopeptide bond. The adherence of the C-terminal AgI/II fragments to the putative tooth surface receptor salivary agglutinin (SAG), as monitored by surface plasmon resonance, indicated that the minimal region of binding was contained within the first and second DE-variant-IgG domains (C 1 and C 2 ) of the C terminus. The minimal C-terminal region that could inhibit S. mutans adherence to SAG was also confirmed to be within the C 1 and C 2 domains. Competition experiments demonstrated that the C-and N-terminal regions of AgI/II adhere to distinct sites on SAG. A cleft formed at the intersection between these C 1 and C 2 domains bound glucose molecules from the cryo-protectant solution, revealing a putative binding site for its highly glycosylated receptor SAG. Finally, electron microscopy images confirmed the elongated structure of AgI/II and enabled building a composite tertiary model that encompasses its two distinct binding regions.Dental caries (also called tooth decay or dental cavities) is a ubiquitous worldwide disease that affects humans of all age groups. Streptococcus mutans, a primary etiological agent of human dental caries (1) and an increasingly recognized cause of bacterial endocarditis (2), adheres to proteins contained within the salivary pellicle on the tooth surface, the extracellular matrix, and other microbial species (3). Antigen I/II (AgI/II, 2 also known as P1, B, SpaP, or PAc) of S. mutans has been implicated in bacterial adherence to constituents of the salivary pellicle (4, 5) and has been studied for the past three decades as a target for protective immunity against dental caries. Apart from adherence, AgI/II influences biofilm formation (6) and promotes platelet aggregation (7), collagen-dependent bacterial invasion of dentin (8), and cariogenicity (9). Although AgI/II was initially discovered on oral streptococci, it has also been identified in members of the Group A and Group B streptococci (10), suggesting a role for this adhesin in a variety of species.The AgI/II family proteins range from 140 to 180 kDa in predicted size and have a primary sequence composed of multiple conserved regions (Fig. 1b). Toward the N terminus, repeated sequences of high alanine content constitute the alanine-rich region followed by a segment commonly referred to as the variable (V) region. Further C-terminal in the sequence is a region of high proline content that forms a repetitive prolinerich region. Following the AgI/II proline-rich region is a C-terminal region (60 kDa or 550 amino acids), which is the most conserved region of AgI/II, with 62% identity ...

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Synthetic Biology: A New Tool for the Trade

Zakeri

2015

ChemBioChem

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Protein-protein interactions are fundamental to many biological processes. Yet, the weak and transient noncovalent bonds that characterize most protein-protein interactions found in nature impose limits on many bioengineering experiments. Here, a new class of genetically encodable peptide-protein pairs--isopeptag-N/pilin-N, isopeptag/pilin-C, and SpyTag/SpyCatcher--that interact through autocatalytic intermolecular isopeptide bond formation is described. Reactions between peptide-protein pairs are specific, robust, orthogonal, and able to proceed under most biologically relevant conditions both in vitro and in vivo. As fusion constructs, they provide a handle on molecules of interest, both organic and inorganic, that can be grasped with an iron grip. Such stable interactions provide robust post-translational control over biological processes and open new opportunities in synthetic biology for engineering programmable and self-assembling protein nanoarchitectures.

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Structure of the C-terminal domain of the surface antigen SpaP from the caries pathogenStreptococcus mutans

Cited by 17 publications

References 14 publications

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

Synthetic Biology: A New Tool for the Trade

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