{"id":410,"date":"2018-01-10T13:50:17","date_gmt":"2018-01-10T12:50:17","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/en\/?page_id=410"},"modified":"2024-02-16T13:58:03","modified_gmt":"2024-02-16T12:58:03","slug":"apvv-0139-06","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/en\/projects\/completed-projects\/apvv-0139-06\/","title":{"rendered":"APVV-0139-06"},"content":{"rendered":"<p><script type=\"text\/javascript\">\n<!--\nfunction launch(newURL, newName, newFeatures, orgName) {\n  var remote = open(newURL, newName, newFeatures);\n  if (remote.opener == null)\n    remote.opener = window;\n  remote.opener.name = orgName;\n  return remote;\n}\n\nfunction launchRemote(name) {\n  var address =  name;\n  myRemote = launch(address ,\n                    \"Okno\",\n                    \"height=500, width=850, left=50, top=50, alwaysLowered=0, alwaysRaised=0, channelmode=0, dependent=0, directories=0, fullscreen=0, hotkeys=1, location=0, menubar=0, resizable=0, scrollbars=0, status=0, titlebar=1, toolbar=0, z-lock=0\",\n                    \"myWindow\");\n}\n\/\/ -->>\n<\/script><\/p>\n<h2>SaFRyR: Structure-function relationships of the ryanodine receptor domains involved in CPVT arrhythmias&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<button onclick=\"goBack()\">Back<\/button> <\/h2>\n<p><script>\t \t \nfunction goBack() { window.history.go(-1); }\t \t \n<\/script><\/p>\n<table border=\"0\" width=\"100%\" cellspacing=\"1\" cellpadding=\"2\">\n<tbody>\n<tr>\n<td>\n<h3>Principal Investigator: Jozef Sevcik<\/h3>\n<h3>Duration: February 2007 &#8211; December 2009<br \/>\nCoordinating Organization: Institute of Molecular Biology SAS, Bratislava<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Annotation:<\/span><\/h3>\n<p>Proper regulation of ryanodine receptors (RyRs) is central to maintaining Ca2+ homeostasis in the periodically contracting myocytes. This regulation is impaired in genetic diseases CPVT-1 and ARVD-2, in which RyRs have mutations. We will determine the structure of two specific RyR domains from regions with frequent occurrence of CPVT\/ARVD mutations (\u201cdomain switch\u201d), important from the viewpoint of allosteric regulation of channel opening, and study their role in modulating resting RyR activity. The structure of the domains as well as of their complex will be determined. The effect of peptide fragments derived from the domains on resting RyR activity will by studied electrophysiologically and by confocal microscopy. The mechanism of interaction between individual functional modules of the RyR will be dissected using allosteric models of RyR activity. Successful completion of the project , i.e., determination of the structure and the principle of function of the domains will enable deeper understanding of &#8220;domain switch&#8221; function and of molecular mechanisms leading to CPVT arrhythmias.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Keywords:<\/span><\/h3>\n<p>Excitation-contraction coupling, CPVT arrhythmias, ryanodine receptor, protein structure, calcium signaling<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Objectives:<\/span><\/h3>\n<ul>\n<li>\n\tTo verify the hypothesis that interaction between the N-terminal and the central domain of the &#8220;domain switch&#8221; is mediated via amino acids, whose mutations cause CPVT-1 and\/or ARVD-2.\n\t<\/li>\n<li>\n\tTo verify the hypothesis that defect in the interaction between the N-terminal and the central domain result in increased resting activity of the RyR.\n\t<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Publications:<\/span><\/h3>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<table class=\"list\" border=\"0\" width=\"100%\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22890710\")'><img decoding=\"async\" class=\"alignnone wp-image-1113\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JPhysiol3.jpg\" alt=\"JPhysiol3\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\"><strong>Janicek R<\/strong>, <strong>Zahradnikova-Jr A<\/strong>, <strong>Polakova E<\/strong>, <strong>Pavelkova J<\/strong>, <strong>Zahradnik I<\/strong>, <strong>Zahradnikova A<\/strong> (2012): <a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22890710\")'>Calcium spike variability in cardiac myocytes results from activation of small cohorts of RYR2 channels.<\/a> <i>J Physiol<\/i> 590: 5091-5106.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22851674\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1114\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JGP-125x150.jpg\" alt=\"JGP\" width=\"75\" height=\"98\" \/><\/a><\/td>\n<td class=\"two\"><strong>Tencerova B<\/strong>, <strong>Zahradnikova A<\/strong>, <strong>Gaburjakova J,<\/strong> <strong>Gaburjakova M<\/strong> (2012): <a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22851674\")'>Luminal Ca2+ controls activation of the cardiac ryanodine receptor by ATP<\/a>. <i>J Gen Physiol<\/i> 140: 93-108.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22781817\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/GPB.jpg\" width=\"75\" height=\"104\" \/><\/a><\/td>\n<td class=\"two\"><strong>Nichtova Z<\/strong>, <strong>Novotova M<\/strong>, Kralova E, Stankovicova T (2012): <a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22781817\")'>Morphological and functional characteristics of models of experimental myocardial injury induced by isoproterenol<\/a>. <i>Gen Physiol Biophys<\/i> 31: 141-51.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20045464?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone\" src=\"http:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S1046592810X00043-cov150h.gif\" width=\"75\" height=\"104\" \/><\/a><\/td>\n<td class=\"two\">Bauerova-Hlinkova V, Hostinova E, Gasperik J, Beck K, Borko L, Lai FA, <strong> Zahradnikova A<\/strong>, Sevcik J (2010): <a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20045464?dopt=Citation\")'>Bioinformatic mapping and production of recombinant N-terminal domains of human cardiac ryanodine receptor 2.<\/a>. <i>Protein Expr. Purif<\/i> 71:33-41.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20974774?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1114\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JGP-125x150.jpg\" alt=\"JGP\" width=\"75\" height=\"98\" \/><\/a><\/td>\n<td class=\"two\"><strong> Zahradnikova A<\/strong>, <strong> Gaburjakova M<\/strong> Bridge JHB, <strong> Zahradnik I<\/strong> (2010): <a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20974774?dopt=Citation\")'>Challenging quantal calcium signaling in cardiac myocytes.<\/a>. <i>J Gen Physiol<\/i> 136:581-583.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20548054\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1114\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JGP-125x150.jpg\" alt=\"JGP\" width=\"75\" height=\"98\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnikova A<\/strong>, <strong>Valent I<\/strong>, <strong>Zahradnik I<\/strong> (2010): <a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20548054\")'>Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating.<\/a> <i> J Gen Physiol<\/i> 136: 101-116.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>SaFRyR: Structure-function relationships of the ryanodine receptor domains involved in CPVT arrhythmias&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Back Principal Investigator: Jozef Sevcik Duration: February 2007 &#8211; December 2009 Coordinating Organization: Institute&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/en\/projects\/completed-projects\/apvv-0139-06\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":199,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/410"}],"collection":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/comments?post=410"}],"version-history":[{"count":4,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/410\/revisions"}],"predecessor-version":[{"id":1629,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/410\/revisions\/1629"}],"up":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/199"}],"wp:attachment":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/media?parent=410"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}