Structure and folding of Glucagon-like Peptide 1-7-(7-36)-amide in aqueous trifluoroethanol studied by NMR

Nuclear magnetic resonance (NMR) spectroscopy reveals that higher-order
aggregates of glucagon-like peptide-1-(7-36)-amide (GLP-1) in pure water at pH
2.5 are disrupted by 35% 2,2,2-trifluoroethanol (TFE), and form a stable and
highly symmetric helical self-aggregate. NMR spectra show that the helical
structure is identical to that formed by monomeric GLP-1 under the same
experimental conditions [Chang et al., Magn. Reson. Chem. 37 (2001) 477-483;
Protein Data Bank at RCSB code: 1D0R], while amide proton exchange rates reveal
a dramatic increase of the stability of the helices of the self-aggregate.
Pulsed-field gradient NMR diffusion experiments show that the TFE-induced
helical self-aggregate is a dimer. The experimental data and model calculations
indicate that the dimer is a parallel coiled coil, with a few hydrophobic
residues on the surface that may cause aggregation in pure water. The results
suggest that the coiled coil dimer is an intermediate state towards the
formation of higher aggregates, e.g. fibrils.

Xiaoqing Chang, Danielle Keller, Se?n I.O'Donoghue and Jens J. Led.
"NMR studies of the aggregation of glucagon-like peptide-1: formation of a
symmetric helical dimer."
FEBS Letters 515, 165-170 (2002).

NMR studies of the aggregation of glucagon-like peptide-1: formation of a symmetric helical dimer.

Solution Structure Of Glucagon-Like Peptide-1-(7-36)-Amide In TrifluoroethanolWATER

Crystal Structure Of Glucagon-Like Peptide-1 In Complex With The Extracellular Domain Of The Glucagon-Like Peptide-1 Receptor

preproglucagon, partial [Canis lupus familiaris]

glucagon precursor - pig (fragment) [Sus scrofa domesticus]

glucagon precursor [Canis lupus familiaris]

glucagon preproprotein [Rattus norvegicus]

RecName: Full=Glucagon; Contains: RecName: Full=Glicentin; Contains: RecName: Full=Glicentin-related polypeptide; Short=GRPP; C

PFG self-diffusion experiment with water-sLED pulse