Donnerstag, 15. Februar 2018, 17:00 - 18:00 iCal
Guest Lecture by Victor TSETLIN
Interactions of Cys-loop receptors with neurotoxic peptides, proteins and low molecular weight compounds
UZA 2, Seminarraum 2D 358
Althanstraße 14, Pharmaziegebäude, 1090 Wien
Lecture
The Doctoral Program ION CHANNELS AND TRANSPORTERS AS MOLECULAR DRUG TARGETS („MolTag“) is pleased to invite you to the following lecture
Interactions of Cys-loop receptors with neurotoxic peptides,
proteins and low molecular weight compounds
by Prof.Dr. Victor TSETLIN
Humboldt Awardee, Head of the Dept. of Molecular Basis of Neurosignaling; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry; Russian Academy of Sciences; victortsetlin3f@gmail.com
on: Thursday, February 15th, 2018, 05:00 pm (17:00 Uhr)
at: UZA 2, Althanstr. 14, 1090 Vienna, Seminar room 2D 358
Abstract: The talk is focusing on the Cys-loop ligand-gated ion channels/receptors comprising nicotinic acetylcholine receptors (nAChRs), glycine receptors (GlyR), receptors of ?-aminobutyric acid (GABA-A receptors) and 5HT-3 serotonin ones. Each of them exists as several subtypes differing in the localization and their role in normal functioning and pathologies. Due to high homology, identification of functionally active individual receptor subtypes cannot be reliably performed with antibodies. Much more efficient are neurotoxic peptides and proteins from animal venoms. Naturally-occurring neurotoxins are used as inhibitors of the respective subtypes in electrophysiological experiments, while their radioactive or fluorescent derivatives are excellent tools for identifying and measuring the receptor levels at normal state and diseases (psychiatric, neurodegenerative or muscle dystrophies). Such distinction of receptor subtypes is extremely important since, for example, ?4?2 nAChRs are most heavily involved in nicotine addiction, while ?7 neuronal nAChRs are implicated in the interactions with ?-amyloid peptide, while “non-neuronal” ?7 nAChR regulate anti-inflammatory response and lung cancer cell proliferation. Detailed structural information about the binding sites for neurotoxins obtained by X-ray analysis of their complexes with Cys-loop receptors or receptor models (such as the acetylcholine-binding proteins, AChBPs) may shed light on the possible functional effects of certain mutations associated with diseases and opens the way to new drugs: for example, ?-conotoxins blocking the ?9/?10 nAChRs are considered as possible analgesics. The recent work of speaker, his coworkers and colleagues from abroad on nAChRs and other Cys-loop receptors will be illustrated with the low-molecular weight compounds (including those of marine origin) [1], ?-conotoxins [2,3] , snake venom ?-neurotoxins [2,4,5] and human endogenous proteins that have the same three-finger folding as ?-neurotoxins and regulate the nAChR activities [6,7] .
1. Kasheverov IE, Shelukhina IV, Kudryavtsev DS, Makarieva TN, Spirova EN, Guzii AG, Stonik VA, Tsetlin VI. 6-bromohypaphorine from marine nudibranch mollusk Hermissenda crassicornis is an agonist of human ?7 nicotinic acetylcholine receptor. Mar Drugs. 2015 Mar 12;13(3):1255-66
2. Dutertre S, Nicke A, Tsetlin VI. Nicotinic acetylcholine receptor inhibitors derived from snake and snail venoms.
Neuropharmacology. 2017 Jun 13. pii: S0028-3908
3. Kasheverov IE, Chugunov AO, Kudryavtsev DS, Ivanov IA, Zhmak MN, Shelukhina IV, Spirova EN, Tabakmakher VM, Zelepuga EA, Efremov RG, Tsetlin VI. High-Affinity ?-Conotoxin PnIA Analogs Designed on the Basis of the Protein Surface Topography Method. Sci Rep. 2016 Nov 14;6:36848.
4.Calcium imaging with genetically encoded sensor Case12: Facile analysis of ?7/?9 nAChR mutants.
Shelukhina I, Spirova E, Kudryavtsev D, Ojomoko L, Werner M, Methfessel C, Hollmann M, Tsetlin V.
PLoS One. 2017 Aug 10;12(8):e0181936.
5. Kudryavtsev DS, Shelukhina IV, Son LV, Ojomoko LO, Kryukova EV, Lyukmanova EN, Zhmak MN, Dolgikh DA, Ivanov IA, Kasheverov IE, Starkov VG, Ramerstorfer J, Sieghart W, Tsetlin VI, Utkin YN. . Neurotoxins from snake venoms and ?-conotoxin ImI inhibit functionally active ionotropic ?-aminobutyric acid (GABA) receptors
J Biol Chem. 2015 Sep 11;290(37):22747-58
6. Tsetlin VI. Three-finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: pharmacological tools and endogenous modulators. Trends Pharmacol Sci. 2015 Feb;36(2):109-23
7. Durek T, Shelukhina IV, Tae HS, Thongyoo P, Spirova EN, Kudryavtsev DS, Kasheverov IE, Faure G, Corringer PJ, Craik DJ, Adams DJ, Tsetlin VI. Interaction of Synthetic Human SLURP-1 with the Nicotinic Acetylcholine Receptors. Sci Rep. 2017 Nov 30;7(1):16606
Biosketch:
Victor Tsetlin has got Ph.D. and D.Sci degrees in chemistry (1973, 1987) at the Shemyakin-Ovchinnikov Institute; now Head of the Department of Molecular Basis of Neurosignaling. Professor (1996) and corresponding member of the Russian Academy of Sciences (2006). The awards: Russian State Prize in Science and Technology (1985), the Humboldt Prize (1992); invited scientist at the Uppsala University, Imperial College (London), Institute of Protein Research (Osaka), Free University (Berlin). Member of the Advisory Board of FEBS J. (2000-2011), Biochem J. (2013-present). Published over 200 papers: in PNAS, Neuron, Nature Str. Mol.Biol, J.Biol.Chem., J Neurochemistry, TIPS, Sci.Rep., Neuropharmacology
Zur Webseite der Veranstaltung
Veranstalter
Doktoratskolleg "Molecular Drug Targets"
Kontakt
Susanne Menschik-Zunzer
Department of Pharmacology and Toxicology, UZA 2
DK Molecular Drug Targets
01 4277 55320
susanne.menschik-zunzer@univie.ac.at, office.moltag@univie.ac.at
Erstellt am Donnerstag, 18. Januar 2018, 12:25
Letzte Änderung am Mittwoch, 24. Januar 2018, 09:01