IndraLab

Statements


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sparser
"A recent study suggests that binding of NADase to SLO stabilizes both toxins, thereby increasing host cell toxicity [ xref ]."

sparser
"Specifically, we studied the interaction of NADase with its cotoxin, SLO."

sparser
"In this study, we tested that hypothesis by examining the physical and functional interactions between SLO and NADase."

reach
"These observations provide an explanation for conservation of full-length NADase expression even when it lacks enzymatic activity and suggest a critical role for binding of NADase to SLO in GAS pathogenesis."

sparser
"We used BLI to investigate in more detail the interaction between NADase and SLO."

reach
"Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations."

sparser
"Emergence of a globally dominant invasive GAS M-type 1 clone in the 1980s was temporally associated with acquisition of DNA sequences encoding enzymatically active NADase and a highly active promoter driving expression of the NADase-SLO operon [ xref , xref ]."

sparser
"The second phase could represent nonspecific binding, or it could reflect two domains of NADase interacting with SLO or a conformational change induced by the initial interaction ( xref )."

reach
"SEC-MALS analysis of the NADase and SLO complex at the same concentrations again revealed a shift in the NADase elution volume and a calculated average mass for the NADase and SLO complex of 83kDa."

sparser
"Purified recombinant SLO bound NADase in vitro, supporting a specific, physical interaction of the two proteins."

reach
"This study characterizes the binding interaction between NADase and SLO and reports that the expression of each toxin is crucial for maximal expression and stability of the other."

sparser
"We therefore propose that the interaction between SLO and NADase in solution stabilizes both toxins and represents an important early step of CMT."

sparser
"We conclude that binding of NADase to SLO stabilizes both toxins, thereby enhancing GAS virulence."

sparser
"When NADase and pneumolysin were loaded on the column together, no shift in the NADase elution volume was observed, suggesting a lack of interaction with pneumolysin ( xref ) and specificity of NADase binding to SLO."

reach
"A new paradigm for the interaction of NADase and SLO was proposed by Madden et al., who found that NADase could be translocated into the cytosol of epithelial cells in vitro after its secretion from GAS bound to the cell surface [XREF_BIBR]."

reach
"Translocation required the concomitant expression of SLO, which suggested a model in which NADase associates with SLO on the epithelial cell surface and is transferred across the cell membrane in a process dependent on SLO."

reach
"Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection."

sparser
"BLI data for the interaction of full-length NADase with SLO fit a binding model with two phases."

sparser
"Our data are consistent with a model whereby interactions of the NADase glycohydrolase domain and translocation domain with SLO and the cell surface increase avidity of NADase binding and facilitate toxin-toxin and toxin-cell surface interactions."

sparser
"Translocation required the concomitant expression of SLO, which suggested a model in which NADase associates with SLO on the epithelial cell surface and is transferred across the cell membrane in a process dependent on SLO."

reach
"Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection."

sparser
"These observations provide an explanation for conservation of full-length NADase expression even when it lacks enzymatic activity and suggest a critical role for binding of NADase to SLO in GAS pathogenesis."

sparser
"This study characterizes the binding interaction between NADase and SLO and reports that the expression of each toxin is crucial for maximal expression and stability of the other."

reach
"We used BLI to investigate in more detail the interaction between NADase and SLO."

sparser
"In the present investigation, we used analytical gel filtration to detect binding in solution between SLO and full-length NADase, as well as binding of SLO to the catalytic domain of NADase (190NADase) at micromolar concentrations."

sparser
"Our data suggested an interaction between SLO and NADase in the culture supernatant, likely after secretion of the toxins, leading to mutual protection from further processing or degradation."

sparser
"A new paradigm for the interaction of NADase and SLO was proposed by Madden et al ., who found that NADase could be translocated into the cytosol of epithelial cells in vitro after its secretion from GAS bound to the cell surface [ xref ]."

reach
"The column was calibrated with proteins of standard masses, and the Stokes radius of NADase alone and the NADase and SLO complex were determined to be consistent with globular protein masses of 59.5 kDa (predicted molecular mass, 47.2 kDa) and 136.3 kDa (predicted molecular mass of SLO + NADase, 110kDa), respectively."

sparser
"This successful clade is characterized by the absence of the hasABC locus and the presence of an nga-ifs-slo locus variant associated with increased expression of NADase and SLO, possibly acquired from emm 1 or emm 12 strains by horizontal gene transfer ( xref , xref )."

reach
"We conclude that binding of NADase to SLO stabilizes both toxins, thereby enhancing GAS virulence."

reach
"In this study, we tested that hypothesis by examining the physical and functional interactions between SLO and NADase."

sparser
"In human epithelial keratinocytes exposed to GAS in vitro , SLO and NADase production is associated with increased GAS intracellular survival ( xref , xref )."

sparser
"SLO and NADase interact in solution as a heterodimer with 1:1 stoichiometry."

sparser
"Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection."

reach
"When NADase and pneumolysin were loaded on the column together, no shift in the NADase elution volume was observed, suggesting a lack of interaction with pneumolysin (XREF_FIG) and specificity of NADase binding to SLO."

reach
"Purified recombinant SLO bound NADase in vitro, supporting a specific, physical interaction of the two proteins."

sparser
"Production of both NADase and SLO is associated with augmented host cell injury beyond that produced by SLO alone, but the mechanism of enhanced cytotoxicity is not known."

sparser
"How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question."

reach
"Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model."