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Impact of Hydrostatic Pressure on an Intrinsically Disordered Protein: A High‐Pressure NMR Study of α‐Synuclein
Author(s) -
Roche Julien,
Ying Jinfa,
Maltsev Alexander S.,
Bax Ad
Publication year - 2013
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300244
Subject(s) - chemistry , chemical shift , polyproline helix , ramachandran plot , population , hydrostatic pressure , bar (unit) , crystallography , protein structure , thermodynamics , peptide , biochemistry , physics , demography , sociology , meteorology
The impact of pressure on the backbone 15 N, 1 H and 13 C chemical shifts in N‐terminally acetylated α‐synuclein has been evaluated over a pressure range 1–2500 bar. Even while the chemical shifts fall very close to random coil values, as expected for an intrinsically disordered protein, substantial deviations in the pressure dependence of the chemical shifts are seen relative to those in short model peptides. In particular, the nonlinear pressure response of the 1 H N chemical shifts, which commonly is associated with the presence of low‐lying “excited states”, is much larger in α‐synuclein than in model peptides. The linear pressure response of 1 H N chemical shift, commonly linked to H‐bond length change, correlates well with those in short model peptides, and is found to be anticorrelated with its temperature dependence. The pressure dependence of 13 C chemical shifts shows remarkably large variations, even when accounting for residue type, and do not point to a clear shift in population between different regions of the Ramachandran map. However, a nearly universal decrease in 3 J HN–Hα by 0.22±0.05 Hz suggests a slight increase in population of the polyproline II region at 2500 bar. The first six residues of N‐terminally acetylated synuclein show a transient of approximately 15 % population of α‐helix, which slightly diminishes at 2500 bar. The backbone dynamics of the protein is not visibly affected beyond the effect of slight increase in water viscosity at 2500 bar.