Monitoring early-stage β-amyloid dimer aggregation by histidine site-specific two-dimensional infrared spectroscopy in a simulation study

Chatterjee, Sompriya; Nam, Yeonsig; Salimi, Abbas; Lee, Jin Yong

doi:10.1039/d2cp02479a

Cited by 4 publications

(2 citation statements)

References 99 publications

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“…Beta-rich Aβ42 oligomers ranging from elongated to compact shapes were described by ss-NMR spectroscopy, ion mobility separation coupled to mass spectrometry, and simulations, featuring multiple interfaces, mixed parallel/antiparallel strands, perpendicular β-sheets and β-barrels. 6,7,11,28,[45][46][47][48][49] For instance, atomistic simulations in explicit solvent revealed β-barrel motifs in Aβ42 trimer and tetramer. 48,50,51 An hexamer peptide barrel was found experimentally to be the building block of Aβ protofibrils.…”

Section: Random Coil Oligomers With β-Sheet Contentmentioning

confidence: 99%

Metastable alpha‐rich and beta‐rich conformations of small Aβ42 peptide oligomers

2023

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Probing the structures of amyloid‐β (Aβ) peptides in the early steps of aggregation is extremely difficult experimentally and computationally. Yet, this knowledge is extremely important as small oligomers are the most toxic species. Experiments and simulations on Aβ42 monomer point to random coil conformations with either transient helical or β‐strand content. Our current conformational description of small Aβ42 oligomers is funneled toward amorphous aggregates with some β‐sheet content and rare high energy states with well‐ordered assemblies of β‐sheets. In this study, we emphasize another view based on metastable α‐helix bundle oligomers spanning the C‐terminal residues, which are predicted by the machine‐learning AlphaFold2 method and supported indirectly by low‐resolution experimental data on many amyloid polypeptides. This finding has consequences in developing novel chemical tools and to design potential therapies to reduce aggregation and toxicity.

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Section: Random Coil Oligomers With β-Sheet Contentmentioning

confidence: 99%

Metastable alpha‐rich and beta‐rich conformations of small Aβ42 peptide oligomers

2023

View full text Add to dashboard Cite

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Section: ρανδομ ὃιλ ολιγομερς ωιτη β-σηεετ ςοντεντmentioning

confidence: 99%

Metastable Alpha-rich and Beta-rich Conformations of Small Aβ42 Peptide Oligomers

Derreumaux

Nguyen

Sterpone

2022

Preprint

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Probing the structures of amyloid-beta (Aβ) peptides in the early steps of aggregation is extremely difficult experimentally and computationally. Yet, this knowledge is extremely important as small oligomers are the most toxic species. Experiments and simulations on Aβ42 monomer point to random coil conformations with either transient helical or β-strand content. Our current conformational description of small Aβ42 oligomers is funneled toward amorphous aggregates with some β-sheet content and rare excited states with well-ordered assemblies of β-sheets. In this study, we emphasize another view based on metastable α-helix bundle oligomers spanning the C-terminus residues which are predicted by the machine-learning AlphaFold2 method and supported indirectly by low-resolution experimental data on many amyloid polypeptides. This finding has consequences in designing drugs to reduce aggregation and toxicity.

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Histidine tautomerism-mediated transthyretin amyloidogenesis: A molecular insight

Chatterjee

Salimi

Lee

2023

Archives of Biochemistry and Biophysics

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Monitoring early-stage β-amyloid dimer aggregation by histidine site-specific two-dimensional infrared spectroscopy in a simulation study

Abstract: Monitoring early-stage β-amyloid (Aβ) dimerization is a formidable challenge for understanding neurological diseases. We compared β-sheet formation and histidine site-specific two-dimensional infrared (2D IR) spectroscopic signatures of Aβ dimers with...

Cited by 4 publications

References 99 publications

Metastable alpha‐rich and beta‐rich conformations of small Aβ42 peptide oligomers

Metastable alpha‐rich and beta‐rich conformations of small Aβ42 peptide oligomers

Metastable Alpha-rich and Beta-rich Conformations of Small Aβ42 Peptide Oligomers

Histidine tautomerism-mediated transthyretin amyloidogenesis: A molecular insight

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