Abstract
Elucidating the structural details of proteins is highly valuable and important for the proper understanding of protein function. In the case of intrinsically disordered proteins (IDPs), however, obtaining the structural details is quite challenging, as the traditional structural biology tools have only limited use. Nuclear magnetic resonance (NMR) is a unique experimental tool that provides ensemble conformations of IDPs at atomic resolution, and when studying IDPs, a slightly different experimental strategy needs to be employed than the one used for globular proteins. We address this point by reviewing many NMR investigations carried out on the α-synuclein protein, the aggregation of which is strongly correlated with Parkinson’s disease.
Highlights
Alpha-synuclein is a presynaptic terminal protein that is localized at the nuclear envelope and presynaptic nerve terminals [1,2]
The fibrillary aggregates of αS have a characteristic cross-β structure consisting of β-sheets, where the individual β-strands are perpendicular to the axis of the fibril [10,11,12]
These fibrillary aggregates are morphologically similar to the amyloid fibrils found in Alzheimer’s disease neuritic plaques and in deposits associated with other amyloidogenic diseases [13,14]
Summary
Alpha-synuclein (αS) is a presynaptic terminal protein that is localized at the nuclear envelope and presynaptic nerve terminals [1,2]. Because in-cell NMR data used to generate Figure 1c were obtained inside E. coli cells without enzymatic acetylation, we can safely rule out the effect of acetylation on αS conformation Another possibility is that the higher N-terminal helicity observed in this in-cell report is due to the fact that only carbonyl chemical shifts were used in computing the SSP scores in the N-terminal region as Cα and Cβ chemical shifts were not available. The same is true even for IDPs as was seen in VP16 TAD and 4EBP1/2; slightly different sample conditions did not influence the results in terms of the presence and/or location of PreSMos. why do the results of different NMR studies on αS conformation not completely agree regarding the location and the degree of pre-population of transient structures?
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