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3D Solution Structure of –Conotoxin MII by NMR Spectroscopy: Effects of Solution Environment on Helicity. Hill, Oomen, Miranda, Bingham, Alewood, and Craik Biochemistry 1998 , 37 , 15621-15630 Presented by Charles Vaske. Conus Magus. Baldomero Olivera, University of Utah.
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3D Solution Structure of –Conotoxin MII by NMR Spectroscopy: Effects of Solution Environment on Helicity Hill, Oomen, Miranda, Bingham, Alewood, and Craik Biochemistry1998, 37, 15621-15630 Presented by Charles Vaske
Conus Magus Baldomero Olivera, University of Utah
Nicotinic Acetlycholine Receptor • Pentameric gated ion channel • Present in muscle and neuronal tissue • Diverse neuronal species • Implicated in schizophrenia, addiciton, AD, Parkinson’s Tourette’s Tsigelny, et al, UCSD
-Conotoxin MII • Antagonist specific to 32 nAChR • Only known inhibitor specific to a single nAChR species • Structure previously unknown • Some homologous structures known
-Conotoxins ** Structure solved
Structure Determination 3 NMR solutions: • 10% D20 / 90% H20 • 30% Deuterated Acetonitrile (CD3CN) • 30% Trifluoroethanol (TFE) NOESY, TOCSY, DQF-COSY One proline residue
TFE H20 CD3CN Figure 4 - NOE peak summaries
Figure 6 - 3D Structure 20 Final Structures
Amphipathic helix Solvent Exposed Buried
MII GCCSNPVCHLEHSNLC* PnIB GCCSLPPCALSNPDYC* Figure 8 - Comparison to PnIb RMSD 0.94Å
Conclusions • Single main conformation • Hydrophobic environment tightens secondary structure • Can form hypotheses about binding to nAChR