Probing the secondary structure of individual Aβ40 amorphous aggregates and fibrils by AFM-IR spectroscopy
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Probing the secondary structure of individual Aβ40 amorphous aggregates and fibrils by AFM-IR spectroscopy. / Herzberg, Mikkel; Szunyogh, Daniel; Thulstrup, Peter W; Hassenkam, Tue; Hemmingsen, Lars.
In: ChemBioChem, 2020, p. 3521-3524.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Probing the secondary structure of individual Aβ40 amorphous aggregates and fibrils by AFM-IR spectroscopy
AU - Herzberg, Mikkel
AU - Szunyogh, Daniel
AU - Thulstrup, Peter W
AU - Hassenkam, Tue
AU - Hemmingsen, Lars
N1 - © 2020 Wiley-VCH GmbH.
PY - 2020
Y1 - 2020
N2 - Structural characterization of aggregates and fibrils of the Aβ protein is pivotal to the molecular level elucidation of Alzheimer's disease (AD). AFM-IR provides nanoscale resolution, and thus allows for spectroscopic interrogation of individual aggregates and fibrils. During aggregation of Aβ we observed mainly disordered Aβ at t=15 min, substantial structural diversity including co-existence of parallel and antiparallel β-sheets within a large amorphous aggregate at t=2 hours, while fibrils exhibited the expected signature of parallel β-sheets at t=1 week. The resonance observed for parallel β-sheets at t=2 hours coincides with that observed for fibrils (at 1634 cm-1), indicating that fibril-like species exist within the large aggregates. Thus, nucleation might occur within such species, in analogy to current theories of protein crystallization where nucleation occurs within large protein clusters. Cu2+ perturbs Aβ aggregation, catalysing rapid formation of amorphous aggregates with diverse secondary structure, but inhibiting fibril growth.
AB - Structural characterization of aggregates and fibrils of the Aβ protein is pivotal to the molecular level elucidation of Alzheimer's disease (AD). AFM-IR provides nanoscale resolution, and thus allows for spectroscopic interrogation of individual aggregates and fibrils. During aggregation of Aβ we observed mainly disordered Aβ at t=15 min, substantial structural diversity including co-existence of parallel and antiparallel β-sheets within a large amorphous aggregate at t=2 hours, while fibrils exhibited the expected signature of parallel β-sheets at t=1 week. The resonance observed for parallel β-sheets at t=2 hours coincides with that observed for fibrils (at 1634 cm-1), indicating that fibril-like species exist within the large aggregates. Thus, nucleation might occur within such species, in analogy to current theories of protein crystallization where nucleation occurs within large protein clusters. Cu2+ perturbs Aβ aggregation, catalysing rapid formation of amorphous aggregates with diverse secondary structure, but inhibiting fibril growth.
U2 - 10.1002/cbic.202000632
DO - 10.1002/cbic.202000632
M3 - Journal article
C2 - 33027846
SP - 3521
EP - 3524
JO - ChemBioChem
JF - ChemBioChem
SN - 1439-4227
ER -
ID: 249626251