"IAA5020406" . " mechanism of membrane translocation" . . "Penetration of adenylate cyclase toxin (ACT) into target cells is a unique example of direct translocation of a toxic enzyme across the target cytoplasmic membrane. Its understanding is, hence, of general relevance for deciphering the principles of membrane interactions of proteins. We will tie-up on identification of functional domains of ACT and use a set of ACT mutants selectively blocked in the individual steps of ACT interaction with cells, in order to define the molecular mechanisms underlying membrane insertion and translocation of ACT. Structures involved in binding of ACT to the CD11b integrin receptor will be defined and the oligomeric status, membrane topology, mechanism of formation and signaling role of ACT channels in calcium mobilization into cells will be determined by an array of biochemical, molecular biology and biophysical approaches. The relationship between ACT structure and membrane activities and induction of leukocyte apoptosis will be deduced."@en . "Byl pops\u00E1n molekul\u00E1rn\u00ED mechanismus interakce AC toxinu s bun\u011B\u010Dnou membr\u00E1nou fagocyt\u016F, objevena jeho nov\u00E1 lektinov\u00E1 aktivita, objasn\u011Bna podstata jeho cytotoxicity a Identifikov\u00E1ny kl\u00ED\u010Dov\u00E9 struktury \u0159\u00EDd\u00EDc\u00ED translokaci AC dom\u00E9ny a tvorbu toxinov\u00FDch kan\u00E1l\u016F."@cs . . "0"^^ . "Pr\u016Fnik adenyl\u00E1t-cykl\u00E1zov\u00E9ho toxinu (ACT) do leukocyt\u016F je unik\u00E1tn\u00EDm p\u0159\u00EDkladem translokace toxick\u00E9ho bakteri\u00E1ln\u00EDho enzymu (AC) p\u0159es plazmatickou membr\u00E1nu c\u00EDlov\u00E9 bu\u0148ky. Jeho detailn\u00ED popis m\u00E1 zna\u010Dn\u00FD v\u00FDznam tak\u00E9 pro pochopen\u00ED obecn\u00FDch mechanism\u016F interakce protein\u016F s biologick\u00FDmi membr\u00E1nami. Nav\u00E1\u017Eeme na p\u0159edchoz\u00ED identifikaci funk\u010Dn\u00EDch dom\u00E9n ACT a p\u0159iprav\u00EDme sadu specifick\u00FDch mutant blokovan\u00FDch v jednotliv\u00FDch kroc\u00EDch interakce ACT s bu\u0148kou, kter\u00E9 vyu\u017Eijeme k identifikaci struktur toxinu \u00FA\u010Dastn\u00EDc\u00EDch se vazby na bun\u011B\u010Dn\u00FD integrinov\u00FD receptor CD11b. Pomoc\u00ED biochemick\u00FDch, molekul\u00E1rn\u011B-biologick\u00FDch a biofyzik\u00E1ln\u00EDch p\u0159\u00EDstup\u016F pak definujeme molekul\u00E1rn\u00ED mechanismy interakce ACT s membr\u00E1nou a translokace AC dom\u00E9ny do bun\u011Bk. Stanov\u00EDme stupe\u0148 oligomerizace a membr\u00E1novou topologii ACT a ur\u010D\u00EDme \u00FAlohu kation-selektivn\u00EDch kan\u00E1l\u016F ACT v mobilizaci v\u00E1pn\u00EDku do bun\u011Bk. Z t\u011Bchto anal\u00FDz posl\u00E9ze vyvod\u00EDme vztah mezi strukturou ACT, sou\u010Dinnost\u00ED jeho membr\u00E1nov\u00FDch aktivit a kapacitou ACT indukovat apopt\u00F3zu leukocyt\u016F." . "2008-02-21+01:00"^^ . "3"^^ . . . "1"^^ . . . "http://www.isvav.cz/projectDetail.do?rowId=IAA5020406"^^ . . . . "14"^^ . " integrin binding" . "14"^^ . . "Mechanismus membr\u00E1nov\u00E9 interakce a cytotoxick\u00E9 aktivity adenyl\u00E1t-cykl\u00E1zov\u00E9ho toxinu" . . "The fundamental molecular mechanism of interaction of AC toxin with phagocytes was described, discovering its novel lectin activity and describing the bais of its cytotoxicity and structures determining AC domain translocation and toxin pore formation."@en . "2008-12-31+01:00"^^ . "2009-07-02+02:00"^^ . "2004-01-01+01:00"^^ . . . . . "Mechanisms of membrane interaction and cytotoxic activity of adenylate cyclase"@en . . "adenylate cyclase toxin" . " protein membrane interactions" . . . "adenylate cyclase toxin; protein membrane interactions; mechanism of membrane translocation; calcium entry; integrin binding; receptor"@en . . " calcium entry" . .