An Ectoprotein Kinase of Group C Streptococci Binds Hyaluronan and Regulates Capsule Formation

Nickel, Volker; Prehm, Sabine; Lansing, Manfred; Mausolf, A.; Podbielski, Andreas; Deutscher, Josef; Prehm, Peter

doi:10.1074/jbc.273.37.23668

Cited by 27 publications

(16 citation statements)

References 32 publications

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“…Proteins with surface-localized binding sites for nucleotides have been reported for cells such as vascular endothelium (40), smooth muscle cells (23), parasites such as Leishmania tropica (26), the amoeba Dictyostelium discoideum (16), and group C streptococci (28). The data presented here describe the first Mg 2ϩ -dependent ATP-binding and -hydrolyzing activity on the external surface of a cell wall-less bacterium.…”

Section: Discussionmentioning

confidence: 77%

OppA, the Substrate-Binding Subunit of the Oligopeptide Permease, Is the Major Ecto-ATPase ofMycoplasma hominis

Miriam

Henrich

2004

J Bacteriol

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Most ATPases, involved in energy-driven processes, act in the cytoplasm. However, external membranebound ATPases have also been described in parasites and eukaryotic cells. In Mycoplasma hominis, a bacterium lacking a cell wall, the surface-exposed substrate-binding protein OppA of an oligopeptide permease (Opp) contains an ATP binding P-loop structure in the C-terminal region. With ATP affinity chromatography and tryptic digestion in the presence or absence of ATP, the functionality of the Mg 2؉ -dependent ATP binding site is demonstrated. In addition to ATP, ADP also could bind to OppA. The presence of an ATPase activity on the surface of M. hominis is indicated by the inactivation of ATP hydrolyzing activity of intact mycoplasma cells by the impermeable ATPase inhibitor 4,4-diisothiocyanostilbene-2,2-disulfonic acid and influenced by the ATP analog 5-fluorosulfonyl-benzoyladenosine. Comparing equimolar amounts of OppA in intact mycoplasma cells and in the purified form indicated that more than 80% of the surface-localized ATPase activity is derived from OppA, implying that OppA is the main ATPase on the surface of mycoplasma cells. Together, these data present the first evidence that the cytoadhesive substrate binding protein OppA of the oligopeptide permease also functions as an ecto-ATPase in Mycoplasma hominis.The most important high-energy phosphate compounds in living cells are adenosine and guanosine triphosphate (ATP and GTP), which serve as carriers of energy that keeps the organism alive. The mobilization of energy is accomplished by a diverse variety of ATPases (31). In 1982, Walker and coworkers (44) described a sequence similarity in the alpha-and beta-subunits of ATP synthetase. This consensus sequence is also found in myosin, kinases, and other ATP-requiring enzymes. The best conserved of these motifs is a glycine-rich region, [AG]-X(4)-G-K- [ST], which typically forms a flexible loop between a beta-strand and an alpha-helix and interacts extensively with the ␤-and ␥-phosphates of the nucleotide, whereas only limited interactions engaged with the ATP adenine ring. This sequence motif, which is generally referred to as Walker A sequence or P-loop, is present in numerous ATP-or GTP-binding proteins, including the nucleotide-binding subunits of the well known ATP-binding cassette (ABC) transporter.Besides the highly conserved Walker A motif there is also a less conserved Walker B motif that is involved in attacking the ␥-phosphate bond during ATP hydrolysis. Consequently, substitution in the Walker sequences generally impairs ATP hydrolysis to a greater or lesser extent (38). Besides the two hydrophilic peripheral nucleotide-binding subunits, ABC transporters generally consist of two hydrophobic membranespanning subunits and a substrate-binding protein which has been described only in bacteria (1, 12). In gram negative bacteria the substrate-binding protein is located within the periplasmic space, whereas in gram positive bacteria it is surface exposed and tethered to the membrane via a lipid ancho...

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Section: Discussionmentioning

confidence: 77%

OppA, the Substrate-Binding Subunit of the Oligopeptide Permease, Is the Major Ecto-ATPase ofMycoplasma hominis

Miriam

Henrich

2004

J Bacteriol

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“…For M. tuberculosis, a DNA-binding protein-1 participates in mycobacterium-lung epithelial cell interaction through HA (59). In contrast to group A Streptococcus (46), E. coli does not present HA on its surface but is able to bind HA similar to group C streptococci (60). Because HA is excreted in the urine and accumulates in the bladder upon UTI, E. coli must be coated with HA in vivo.…”

Section: Discussionmentioning

confidence: 99%

Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Rouschop¹,

Sylva²,

Teske³

et al. 2006

The Journal of Immunology

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Escherichia coli is the most common pathogen found in urinary tract infections (UTIs), mainly affecting children and women. We report that CD44, a hyaluronic acid (HA) binding protein that mediates cell-cell and cell-matrix interactions, facilitates the interaction of E. coli with urothelial cells and thus the infection of the host. We found that CD44 is constitutively expressed on urothelial cells and that HA accumulates in E. coli-induced UTI. In CD44-deficient mice, the bacterial outgrowth was dramatically less compared with wild-type mice despite similar granulocyte influx in the bladder and in the kidney as well as comparable cytokines/chemokines levels in both genotypes. E. coli was able to bind HA, which adhered to CD44-positive tubular epithelial cells. Most importantly, the interaction of CD44 on tubular epithelial cells with HA facilitated the migration of E. coli through the epithelial monolayer. The results provide evidence that CD44 on urothelial cells facilitates E. coli UTI. Disruption of the interaction between CD44 and HA in the bladder may provide a new approach to prevent and to treat UTI.

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“…So far only a few of these enzymes have been characterized on the molecular or biochemical level (24, 30 -33). Interestingly, two previously identified proteins, CD4 receptor on T helper cells (34) and a 56-kDa protein from group C streptococci (35), were reported to display ecto-protein kinase activity.…”

mentioning

confidence: 99%

Coordinate Expression of GPEET Procyclin and Its Membrane-associated Kinase in Trypanosoma brucei Procyclic Forms

Schlaeppi

Malherbe

Bütikofer

2003

Journal of Biological Chemistry

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GPEET procyclin is a major glycosylphosphatidylinositol-anchored protein of procyclic (insect stage) trypanosomes in culture and is heavily phosphorylated in the GPEET pentapeptide repeat. The phosphorylation reaction is a late event and occurs during maturation and transport of GPEET or on the parasite surface by an ecto-protein kinase. Initial biochemical characterization of the GPEET kinase activity now shows that it depends on bivalent cations for maximal activity, is stimulated by sulfhydryl group reagents, and is specific for ATP as phosphoryl donor. No kinase activity is detected in bloodstream form trypanosomes in culture, whereas strong phosphorylation is observed in early procyclic forms. In addition, the GPEET kinase activity is absent from procyclic trypanosomes that have repressed GPEET synthesis but can be induced in these same stocks by conditions, which also induce GPEET expression. However, the presence of an active kinase does not depend on the presence of (functional) GPEET because it can be detected in parasites expressing a non-phosphorylatable GPEET mutant protein and in procyclin null mutant trypanosomes. Interestingly, the presence of the glycosylphosphatidylinositol lipid moiety seems necessary for GPEET to become phosphorylated. Together, the results demonstrate that GPEET and its kinase are expressed during the same life cycle stages and that factors that induce the expression of GPEET in vitro also induce the expression of the GPEET kinase.

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An Ectoprotein Kinase of Group C Streptococci Binds Hyaluronan and Regulates Capsule Formation

Cited by 27 publications

References 32 publications

OppA, the Substrate-Binding Subunit of the Oligopeptide Permease, Is the Major Ecto-ATPase ofMycoplasma hominis

OppA, the Substrate-Binding Subunit of the Oligopeptide Permease, Is the Major Ecto-ATPase ofMycoplasma hominis

Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Coordinate Expression of GPEET Procyclin and Its Membrane-associated Kinase in Trypanosoma brucei Procyclic Forms

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