Ramachandran Map Analysis of the Monomeric Aβ 1-40 and Aβ 1-42 Peptides by Solution NMR
2017; Elsevier BV; Volume: 112; Issue: 3 Linguagem: Inglês
10.1016/j.bpj.2016.11.2605
ISSN1542-0086
Autores Tópico(s)Mass Spectrometry Techniques and Applications
ResumoTo explore in detail the structural propensity of the monomeric Aβ1-40 and Aβ1-42 peptides in solution we recorded a large set of NMR parameters, including chemical shifts, NOEs, and J couplings. 3JHNHα couplings were measured with high precision using a recently developed TROSY-based experiment. Systematic comparisons show that at neutral pH the Aβ1-40 and Aβ1-42 peptides populate almost indistinguishable coil-like conformations. NOESY spectra collected at very high resolution remove assignment ambiguities and show no long-range NOE contacts. Six sets of backbone J couplings (3JHNHα, 3JCʹCʹ, 3JC’Hα, 1JHαCα, 2JCαN and 1JCαN) recorded for Aβ1-40 were used as input for the recently developed MERA Ramachandran-map analysis, yielding residue-specific backbone ϕ/ψ torsion angle distributions that closely resemble random coil distributions, the absence of significantly elevated propensity for β-conformations in the C-terminal region of the peptide, and a small but distinct propensity for αL at K28. Our results suggest that the self-association of Aβ peptides into toxic oligomers is not driven by elevated propensities of the monomeric species to adopt β-strand-like conformations. Instead, accelerated disappearance of Aβ NMR signals in D2O over H2O, particularly pronounced for Aβ1-42, suggests that intermolecular interactions between the hydrophobic regions of the peptide dominate the aggregation process.
Referência(s)