The Surface Protein Srr-1 of
            <i>Streptococcus agalactiae</i>
            Binds Human Keratin 4 and Promotes Adherence to Epithelial HEp-2 Cells

Samen, Ulrike; Eikmanns, Bernhard J.; Reinscheid, Dieter J.; Borges, Frédéric

doi:10.1128/iai.00717-07

Cited by 102 publications

(120 citation statements)

References 66 publications

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“…Unlike other endocytotic receptors, such as mannose receptor or CLEC9A, DEC205 usually targets to late endosomes and lysosomes (14,43); thus, DEC205 may also bind keratins on cell debris in phagosomes or early endosomes and transport them to late endosomes and lysosomes for more efficient antigen presentation. It is noteworthy that keratins are not only expressed inside cells, they are also found on the surface of some cell types such as carcinoma cells (30,(48)(49)(50). Evidence shows that extracellular acidification is usually associated with inflammation and tumorigenesis and is treated as a danger signal by the immune system (51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

Cao

Chang

Shi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Clearance of dead cells is critical for maintaining homeostasis and prevents autoimmunity and inflammation. When cells undergo apoptosis and necrosis, specific markers are exposed and recognized by the receptors on phagocytes. DEC205 (CD205) is an endocytotic receptor on dendritic cells with antigen presentation function and has been widely used in immune therapies for vaccine generation. It has been shown that human DEC205 recognizes apoptotic and necrotic cells in a pH-dependent fashion. However, the natural ligand(s) of DEC205 remains unknown. Here we find that keratins are the cellular ligands of human DEC205. DEC205 binds to keratins specifically at acidic, but not basic, pH through its N-terminal domains. Keratins form intermediate filaments and are important for maintaining the strength of cells and tissues. Our results suggest that keratins also function as cell markers of apoptotic and necrotic cells and mediate a pH-dependent pathway for the immune recognition of dead cells. T he immune system is responsible for removing self-antigens such as dead cells to maintain tissue homeostasis and prevent autoimmunity (1-3). Dead cells are recognized and engulfed by phagocytes through their cell surface receptors (4), leading to either immune activation or tolerance (5-8). A number of receptors have been found to be able to mediate the clearance of dead cells (3); for example, CD14 (9), CD36 (10), integrin (11), PtdSerR (12), CLEC9A (13-15), and TIM receptor family members (16). Among known dead cell markers, phosphatidylserine (PS) is the most common one that can be recognized by several receptors such as CD36, PtdSerR, and TIM receptors, and acts as an "eatme" signal for phagocytes mediating dead cell clearance (4). Other than PS, several cellular proteins have also been found to be able to perform the similar function. For example, actin filaments can be recognized by CLEC9A as a damaged cell marker (13, 15). The recognition of different dead cell markers by phagocytes provides an efficient way to remove cell debris completely.Keratins are important cytoskeletal components and form intermediate filaments in cytoplasm. There are 54 known members in the keratin family that are divided into two types based on their isoelectric points and sequences (17). Keratin monomers can assemble into bundles first and then form fibrous filaments ∼10 nm in diameter, which act as a scaffold and provide mechanical support for maintaining the strength and toughness of cells and tissues (18,19). Recently, evidence has accumulated showing that keratins play physiological roles in addition to their structural functions, for example, in cell growth, proliferation, mobility, apoptosis, and tumorigenesis (18,20,21). DEC205 (CD205 or Ly75, molecular mass of 205 kDa) is an endocytotic receptor highly expressed on dendritic cells and thymic epithelial cells (8,22) and capable of inducing either tolerance or immunity in the absence or presence of inflammatory stimuli (23). DEC205 belongs to the mannose receptor family (24), which includes...

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Section: Discussionmentioning

confidence: 99%

Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

Cao

Chang

Shi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…These adhesins contain serine-rich repeats (SRR) that are heavily modified. The glycoproteins are exported from the cell, but remain associated with the cell wall and allow the bacteria to attach to the host cells and their surrounding extracellular matrix (10)(11)(12)(13)(14)(15)(16)(17). In addition, SRR glycoproteins may also mediate interactions between bacteria, facilitating biofilm formation and bacterial colonization (18).…”

mentioning

confidence: 99%

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Chen

Seepersaud

Bensing

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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O-glycosylation of Ser and Thr residues is an important process in all organisms, which is only poorly understood. Such modification is required for the export and function of adhesin proteins that mediate the attachment of pathogenic Gram-positive bacteria to host cells. Here, we have analyzed the mechanism by which the cytosolic O-glycosyltransferase GtfA/B of Streptococcus gordonii modifies the Ser/Thr-rich repeats of adhesin. The enzyme is a tetramer containing two molecules each of GtfA and GtfB. The two subunits have the same fold, but only GtfA contains an active site, whereas GtfB provides the primary binding site for adhesin. During a first phase of glycosylation, the conformation of GtfB is restrained by GtfA to bind substrate with unmodified Ser/Thr residues. In a slow second phase, GtfB recognizes residues that are already modified with N-acetylglucosamine, likely by converting into a relaxed conformation in which one interface with GtfA is broken. These results explain how the glycosyltransferase modifies a progressively changing substrate molecule.

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“…1A) (39,42,52). Upstream of this binding domain, Srr1 displays two non-repeated regions (NR1 and NR2) showing no homology with known proteins which are separated by a first serine-rich region (SR1) where the proportion of the Ser/Thr residues is above 40%.…”

mentioning

confidence: 99%

O-Glycosylation of the N-terminal Region of the Serine-rich Adhesin Srr1 of Streptococcus agalactiae Explored by Mass Spectrometry

Chaze

Guillot

Valot³

et al. 2014

Molecular & Cellular Proteomics

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Serine-rich (Srr) proteins exposed at the surface of Gram-positive bacteria are a family of adhesins that contribute to the virulence of pathogenic staphylococci and streptococci. Lectin-binding experiments have previously shown that Srr proteins are heavily glycosylated. We report here the first mass-spectrometry analysis of the glycosylation of Streptococcus agalactiae Srr1. After Srr1 enrichment and trypsin digestion, potential glycopeptides were identified in collision induced dissociation spectra using X! Tandem. The approach was then refined using higher energy collisional dissociation fragmentation which led to the simultaneous loss of sugar residues, production of diagnostic oxonium ions and backbone fragmentation for glycopeptides. This Protein glycosylation takes place in bacteria. A considerable amount of information on the biochemical pathways involved in protein glycosylation has been obtained in the genera Campylobacter and Neisseria (1-3). Hence, functional studies performed on Gram-negative bacteria have revealed important properties of protein glycosylation pathways. Like in eukaryotes, proteins can be glycosylated on asparagines (N-glycosylation) or serine/threonine residues (O-glycosylation). Two modes of glycan transfer onto proteins have been characterized in Gram-negative bacteria. In the first, the activated glycan is synthesized on a lipid carrier on the cytoplasmic side of the membrane. After membrane translocation, the glycan portion of the polyprenyl-phosphate-glycan intermediate is transferred en bloc to the protein by an oligosaccharyltransferase active in the periplasm. Such mechanism has been demonstrated for N-glycosylation in Campylobacter jejuni (4 -6) and O-glycosylation in Neisseria gonorrheae (7-9). These pathways are responsible for the glycosylation of more than 65 proteins in C. jejuni (10) and 12 different proteins in N.

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The Surface Protein Srr-1 of Streptococcus agalactiae Binds Human Keratin 4 and Promotes Adherence to Epithelial HEp-2 Cells

Cited by 102 publications

References 66 publications

Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

O-Glycosylation of the N-terminal Region of the Serine-rich Adhesin Srr1 of Streptococcus agalactiae Explored by Mass Spectrometry

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