National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Identification of residues of acylated domain of RTX toxins involved in acyltransferase binding
Grobarčíková, Michaela ; Mašín, Jiří (advisor) ; Černý, Ondřej (referee)
Both adenylate cyclase toxin (CyaA) and α-hemolysin (HlyA) are members of Repeats in ToXins (RTX) cytolysins that play key roles in the virulence of Bordetella pertussis and Escherichia coli, respectively. Bacterial RTX toxins represent a growing group of proteins produced by gram- negative bacteria. These pore-forming RTX toxins share several notable common features: (1) they require post-translational activation by attachment of fatty acid chains to two lysine residues; (2) they contain a hydrophobic domain that forms cation-selective pores in target cell membranes; (3) they are secreted by a type I secretion system; (4) after secretion, they become biologically active by binding of Ca2+ to the nonapeptide glycine- and aspartate-rich repeats. CyaA translocates a unique AC enzyme to the cytosol of phagocytes and subverts their bactericidal functions by unregulated conversion of ATP to cAMP. CyaA and HlyA also permeabilize the cell membrane of eukaryotic cells through cation-selective pores. Both toxins preferentially bind to cells expressing β2 integrins but can also interact with a variety of cells that do not express integrins or with naked lipid membranes. Both toxins are activated from protoxin form by post- translational acylation mediated by a specific acyltransferase. CyaA is activated by...
Structure-function relationship of Kingella kingae RtxA toxin.
Růžičková, Eliška ; Osička, Radim (advisor) ; Šulc, Miroslav (referee)
Kingella kingae is a pediatrically significant, facultative pathogen. It asymptomatically colonizes the oropharynx of young children, where it is a part of the normal microflora. However, if it penetrates the respiratory epithelial barrier and begins to spread throughout the body, it can cause serious infectious diseases. Thanks to today's advanced diagnostic methods, K. kingae is included among important human pathogens, and in pediatric patients, K. kingae is reported as a frequent cause of osteoarticular infections, such as osteomyelitis and septic arthritis, bacteremia, and endocarditis. The key virulence factor of this bacterium, the cytotoxin RtxA, belongs to the RTX (Repeats in ToXin) toxin family. This family of toxins shares several characteristic features: (i) the presence of a hydrophobic pore-forming domain in the N-terminal part of the molecule containing several predicted transmembrane α-helices (ii) the inactive protoxin is activated by different types of fatty acids bound to specific lysine residues in the acylated domain, (iii) the presence of nonapeptide repeat sequences, rich in glycine and aspartate residues, that are important for the binding of calcium ions, (iv) the presence of a C-terminal secretion signal that is recognized by the type I secretion system (T1SS), and (v)...

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