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SUMMARY:Insights into unfolded protein states and GPCR function by solutio
 n NMR - Prof. Dr. Stephan Grzesiek\, University of Basel
DTSTART:20161207T103000Z
DTEND:20161207T113000Z
UID:TALK69428@talks.cam.ac.uk
CONTACT:23027
DESCRIPTION:We use extensively residual dipolar coupling\, paramagnetic la
 beling\, hydrogen bond scalar couplings and other NMR and non-NMR paramete
 rs to characterize unfolded protein states in a quantitative manner [1-6].
  Thus we have generated a minimal structural ensemble of urea-denatured ub
 iquitin by constrained structure calculations. The ensemble reveals about 
 10 % native-like local structure in parts of the molecule on the backgroun
 d of long-range Gaussian chain behavior\, thereby resolving Levinthal’s 
 paradox. Recent orthogonal single molecule FRET data show excellent agreem
 ent to this ensemble. Furthermore\, we have obtained atomic details of the
  pressure-assisted\, cold-denatured state of ubiquitin by high-resolution 
 NMR techniques. This state has structural propensities\, which are very si
 milar to ubiquitin’s alcohol-denatured (A-) state. \n\nG protein-coupled
  receptors (GPCRs) are physiologically important transmembrane signaling p
 roteins that trigger intracellular responses upon binding of extracellular
  ligands. Despite recent breakthroughs in GPCR crystallography\, the detai
 ls of ligand-induced signal transduction are not well understood due to mi
 ssing dynamical information. We have recently shown [7] that receptor moti
 ons can be followed at virtually any backbone site in a thermostabilized m
 utant of the turkey 1-adrenergic receptor. I will discuss insights from
  NMR on ligand recognition\, thermostabilization\, signal transduction and
  G-protein binding as well as recently developed strategies for economic i
 sotope labeling in insect cells [8].\n\n\nReferences\n\n[1]	Huang\, J.-R.\
 , Grzesiek\, S.\, J. Am. Chem. Soc. 2010\, 132\, 694–705.\n\n[2]	Nisius\
 , L.\, Grzesiek\, S.\, Nat Chem 2012\, 4\, 711–717.\n\n[3]	Vajpai\, N.\,
  Nisius\, L.\, Wiktor\, M.\, Grzesiek\, S.\, Proc. Natl. Acad. Sci. USA 20
 13\, 110\, E368–76.\n\n[4]	Leung\, H. T. A.\, Bignucolo\, O.\, Aregger\,
  R.\, Dames\, S. A.\, Mazur\, A.\, Bernèche\, S.\, Grzesiek\, S.\, J. Che
 m. Theory Comput. 2016\, 12\, 383–394.\n\n[5]	Bignucolo\, O.\, Leung\, H
 . T. A.\, Grzesiek\, S.\, Bernèche\, S.\, J. Am. Chem. Soc. 2015\, 137\, 
 4300–4303.\n\n[6]	Aznauryan\, M.\, Delgado\, L.\, Soranno\, A.\, Nettels
 \, D.\, Huang\, J.-R.\, Labhardt\, A. M.\, Grzesiek\, S.\, Schuler\, B.\, 
 Proc. Natl. Acad. Sci. USA 2016\, 113\, E5389–E5398.\n\n[7]	Isogai\, S.\
 , Deupi\, X.\, Opitz\, C.\, Heydenreich\, F. M.\, Tsai\, C.-J.\, Brueckner
 \, F.\, Schertler\, G. F. X.\, Veprintsev\, D. B.\, Grzesiek\, S.\, Nature
  2016\, 530\, 237–241.\n\n[8]	Opitz\, C.\, Isogai\, S.\, Grzesiek\, S.\,
  J. Biomol. NMR 2015\, 62\, 373–385.
LOCATION:Department of Chemistry\, Cambridge\, Unilever lecture theatre
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