BEGIN:VCALENDAR VERSION:2.0 PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4// BEGIN:VEVENT UID:20260313T164536EDT-5226Uw0Pri@132.216.98.100 DTSTAMP:20260313T204536Z DESCRIPTION:Dr. Voula Kanelis\nDepartment of Chemical and Physical Sciences \, University of Toronto\nMississauga\n“Biochemical and biophysical studie s of the first nucleotide\nbinding domain of SUR2A”\n \nThe sulfonylurea r eceptor 2A (SUR2A) is an ATP-binding cassette\n(ABC) protein that forms th e regulatory subunit of ATP-sensitive\npotassium (KATP) channels in the he art.  In KATP\nchannels\, four SUR2A proteins surround four pore-forming K ir6.2\nsubunits. Regulation of KATP channel gating is a complex process\nt hat involves both the Kir6.2 and SUR2A subunits. ATP binding at\nthe Kir6. 2 subunits results in closed KATP channels\, whereas ATP\nbinding and hydr olysis at the SUR2A NBDs opens the pore. Additional\nmodes of KATP channel regulation involve phosphorylation by protein\nkinase A of specific sites within the SUR2A NBDs\, with\nmono-phosphorylation of NBD1 or NBD2 result ing in KATP channel\nactivation and di-phosphorylation further stimulating channel\nactivity. Proper regulation of KATP channels by SUR2A is critica l\,\nas mutations in the NBDs that affect ATP hydrolysis and cellular\ntra fficking cause cardiovascular disorders.\nWe have focused our initial stud ies of SUR2A on NBD1. Using\nstructure-based sequence alignments\, predict ions of disordered\nregions\, and biophysical studies\, we determined the domain\nboundaries for SUR2A NBD1 that have enabled\, for the first time\, \nNMR studies of NBD1. Surprisingly our alignment and screening data\nindi cate that SUR2A NBD1 contains two putative\, previously\nunidentified\, re gulatory elements: a large insert within the\nβ-sheet subdomain and a C-te rminal extension that are analogous to\nthe RI and RE in CFTR NBD1\, and m ay be present in other members of\nthe C-subfamily of ABC transporters. NM R data on SUR2A NBD1\nindicate significant protein dynamics that are alter ed with ATP\nbinding and phosphorylation and fluorescence data indicate\nc onformational changes in NBD1 with phosphorylation. These data\nwill be pr esented and discussed in terms of a model that correlates\nstructural chan ges in SUR2A NBD1 to regulation of KATP channel\ngating.\n \nMandatory for Graduate Students\n DTSTART:20110609T200000Z DTEND:20110609T200000Z LOCATION:McIntyre Medical Building\, CA\, QC\, Montreal\, H3G 1Y6\, 3655 pr omenade Sir William Osler SUMMARY:Biochemistry Seminar - Dr. Voula Kanelis URL:/channels/event/biochemistry-seminar-dr-voula-kane lis-174491 END:VEVENT END:VCALENDAR