Observation of β-sheet aggregation in a gas-phase tau-peptide dimer

TY - JOUR

T1 - Observation of β-sheet aggregation in a gas-phase tau-peptide dimer

AU - Vaden, Timothy D.

AU - Gowers, Sally A.N.

AU - Snoek, Lavina C.

PY - 2009/2/25

Y1 - 2009/2/25

N2 - In Alzheimer's disease, the tau protein forms intracellular amyloid fibrils in which the 306VQIVYK311 sequence adopts parallel β-sheets, enabling fibril formation via cross-β steric zippers. We investigated aggregation of the protected segment (Ac-VQIVYK-NHMe) using IR/UV hole-burning spectroscopy in the NH stretch region in a cold molecular beam combined with DFT calculations in order to characterize its structure and identify the noncovalent interactions generally responsible for aggregation and stabilization in amyloid peptides. The computed and experimental IR spectra suggest that the tau-protein fragments form extended β-strands that are combined in a β-sheet through characteristic backbone hydrogen bonds, indicating that this secondary structure is energetically most attractive and readily forms in the gas phase, without any guiding interactions from a solvent or protein environment.

AB - In Alzheimer's disease, the tau protein forms intracellular amyloid fibrils in which the 306VQIVYK311 sequence adopts parallel β-sheets, enabling fibril formation via cross-β steric zippers. We investigated aggregation of the protected segment (Ac-VQIVYK-NHMe) using IR/UV hole-burning spectroscopy in the NH stretch region in a cold molecular beam combined with DFT calculations in order to characterize its structure and identify the noncovalent interactions generally responsible for aggregation and stabilization in amyloid peptides. The computed and experimental IR spectra suggest that the tau-protein fragments form extended β-strands that are combined in a β-sheet through characteristic backbone hydrogen bonds, indicating that this secondary structure is energetically most attractive and readily forms in the gas phase, without any guiding interactions from a solvent or protein environment.

UR - https://www.scopus.com/pages/publications/67749143921

UR - https://www.scopus.com/pages/publications/67749143921#tab=citedBy

U2 - 10.1021/ja807760d

DO - 10.1021/ja807760d

M3 - Article

C2 - 19178142

SN - 0002-7863

VL - 131

SP - 2472

EP - 2474

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 7

ER -