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NMR studies of the aggregation of glucagon‐like peptide‐1: formation of a symmetric helical dimer
Author(s) -
Chang Xiaoqing,
Keller Danielle,
O'Donoghue Seán I.,
Led Jens J.
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02466-3
Subject(s) - dimer , chemistry , peptide , glucagon , biochemistry , organic chemistry , hormone
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.