Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distinguishing amyloid fibril structures in Alzheimer's disease (AD) by two-dimensional ultraviolet (2DUV) spectroscopy.

ABSTRACT: Understanding the aggregation mechanism of amyloid fibrils and characterizing their structures are important steps in the investigation of several neurodegenerative disorders associated with the misfolding of proteins. We report a simulation study of coherent two-dimensional chiral signals of three NMR structures of A? protein fibrils associated with Alzheimer's Disease, two models for A?(8-40) peptide wild-type (WT) and one for the Iowa (D23N) A?(15-40) mutant. Both far-ultraviolet (FUV) signals (? = 190-250 nm), which originate from the backbone n?* and ??* transitions, and near-ultraviolet (NUV) signals (? ? 250 nm) associated with aromatic side chains (Phe and Tyr) show distinct cross-peak patterns that can serve as novel signatures for the secondary structure.

SUBMITTER: Lam AR

PROVIDER: S-EPMC3458647 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Distinguishing amyloid fibril structures in Alzheimer's disease (AD) by two-dimensional ultraviolet (2DUV) spectroscopy.

Lam A R AR Jiang J J Mukamel S S

Biochemistry 20111020 45

Understanding the aggregation mechanism of amyloid fibrils and characterizing their structures are important steps in the investigation of several neurodegenerative disorders associated with the misfolding of proteins. We report a simulation study of coherent two-dimensional chiral signals of three NMR structures of Aβ protein fibrils associated with Alzheimer's Disease, two models for Aβ(8-40) peptide wild-type (WT) and one for the Iowa (D23N) Aβ(15-40) mutant. Both far-ultraviolet (FUV) signal ...[more]

PMID: 21961527

Similar Datasets

Correction: Distinguishing Amyloid Fibril Structures in AlzheimeraAZs Disease (AD) by Two-Dimensional Ultraviolet (2DUV) Spectroscopy

Project description: Not available

| S-EPMC3614493 | biostudies-literature

Simulation of two-dimensional ultraviolet spectroscopy of amyloid fibrils.

Project description:Revealing the structure and aggregation mechanism of amyloid fibrils is essential for the treatment of over 20 diseases related to protein misfolding. Coherent two-dimensional (2D) infrared spectroscopy is a novel tool that provides a wealth of new insight into the structure and dynamics of biomolecular systems. Recently developed ultrafast laser sources are extending multidimensional spectroscopy into the ultraviolet (UV) region, and this opens up new opportunities for probing fibrils. In a simulation study, we show that 2DUV spectra of the backbone of a 32-residue ?-amyloid (A?(9-40)) fibril associated with Alzheimer's disease and two intermediate prefibrillar structures carry characteristic signatures of fibril size and geometry that could be used to monitor its formation kinetics. The dependence of these signals on the fibril size and geometry is explored. We demonstrate that the dominant features of the ?-amyloid fibril spectra are determined by intramolecular interactions within a single A?(9-40), and intermolecular interactions at the "external interface" have clear signatures in the fine details of these signals.

| S-EPMC2953465 | biostudies-literature

Tracking the mechanism of fibril assembly by simulated two-dimensional ultraviolet spectroscopy.

Project description:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of plaque deposits in the human brain. The main component of these plaques consists of highly ordered structures called amyloid fibrils, formed by the amyloid β-peptide (Aβ). The mechanism connecting Aβ and AD is yet undetermined. In a previous study, a coarse-grained united-residue model and molecular dynamics simulations were used to model the growth mechanism of Aβ amyloid fibrils. On the basis of these simulations, a dock/lock mechanism was proposed, in which Aβ fibrils grow by adding monomers at either end of an amyloid fibril template. To examine the structures in the early time-scale formation and growth of amyloid fibrils, simulated two-dimensional ultraviolet spectroscopy is used. These early structures are monitored in the far ultraviolet regime (λ = 190-250 nm) in which the computed signals originate from the backbone nπ* and ππ* transitions. These signals show distinct cross-peak patterns that can be used, in combination with molecular dynamics, to monitor local dynamics and conformational changes in the secondary structure of Aβ-peptides. The protein geometry-correlated chiral xxxy signal and the non-chiral combined signal xyxy-xyyx were found to be sensitive to, and in agreement with, a dock/lock pathway.

| S-EPMC3684205 | biostudies-literature

Two-dimensional infrared spectroscopy reveals the complex behaviour of an amyloid fibril inhibitor.

Project description:Amyloid formation has been implicated in the pathology of over 20 human diseases, but the rational design of amyloid inhibitors is hampered by a lack of structural information about amyloid-inhibitor complexes. We use isotope labelling and two-dimensional infrared spectroscopy to obtain a residue-specific structure for the complex of human amylin (the peptide responsible for islet amyloid formation in type 2 diabetes) with a known inhibitor (rat amylin). Based on its sequence, rat amylin should block formation of the C-terminal ?-sheet, but at 8 h after mixing, rat amylin blocks the N-terminal ?-sheet instead. At 24 h after mixing, rat amylin blocks neither ?-sheet and forms its own ?-sheet, most probably on the outside of the human fibrils. This is striking, because rat amylin is natively disordered and not previously known to form amyloid ?-sheets. The results show that even seemingly intuitive inhibitors may function by unforeseen and complex structural processes.

| S-EPMC3334878 | biostudies-literature

Two-dimensional near-ultraviolet spectroscopy of aromatic residues in amyloid fibrils: a first principles study.

Project description:We report a first principles study of two dimensional electronic spectroscopy of aromatic side chain transitions in the 32-residue β-amyloid (Aβ(9-40)) fibrils in the near ultraviolet (250-300 nm). An efficient exciton Hamiltonian with electrostatic fluctuations (EHEF) algorithm is used to compute the electronic excitations in the presence of environmental fluctuations. The through-space inter- and intra-molecular interactions are calculated with high level quantum mechanics (QM) approaches, and interfaced with molecular mechanics (MM) simulations. Distinct two dimensional near ultraviolet (2DNUV) spectroscopic signatures are identified for different aromatic transitions, and the couplings between them. 2DNUV signals associated with the transition couplings are shown to be very sensitive to the change of residue-residue interactions induced by residue mutations. Our simulations suggest that 2DNUV spectra could provide a useful local probe for the structure and kinetics of fibrils.

| S-EPMC3141107 | biostudies-literature

Near-Ultraviolet Circular Dichroism and Two-Dimensional Spectroscopy of Polypeptides.

Project description:A fully quantitative theory of the relationship between protein conformation and optical spectroscopy would facilitate deeper insights into biophysical and simulation studies of protein dynamics and folding. In contrast to intense bands in the far-ultraviolet, near-UV bands are much weaker and have been challenging to compute theoretically. We report some advances in the accuracy of calculations in the near-UV, which were realised through the consideration of the vibrational structure of the electronic transitions of aromatic side chains.

| S-EPMC7828623 | biostudies-literature

Signatures of the Protein Folding Pathway in Two-Dimensional Ultraviolet Spectroscopy.

Project description:The function of protein relies on their folding to assume the proper structure. Probing the structural variations during the folding process is crucial for understanding the underlying mechanism. We present a combined quantum mechanics/molecular dynamics simulation study that demonstrates how coherent resonant nonlinear ultraviolet spectra can be used to follow the fast folding dynamics of a mini-protein, Trp-cage. Two dimensional ultraviolet signals of the backbone transitions carry rich information of both local (secondary) and global (tertiary) structures. The complexity of signals decreases as the conformational entropy decreases in the course of the folding process. We show that the approximate entropy of the signals provides a quantitative marker of protein folding status, accessible by both theoretical calculations and experiments.

| S-EPMC3999791 | biostudies-literature

Distinguishing gramicidin D conformers through two-dimensional infrared spectroscopy of vibrational excitons.

Project description:Gramicidin D is a short peptide which dimerizes to form helical pores, adopting one of two conformations in the process. These conformations differ primarily in number of residues per turn and the hydrogen-bond registry between rungs of the helix. Using amide I 2D infrared (IR) and FTIR, we have demonstrated that it is possible to distinguish between the different conformers of gramicidin D in solution. We show that the spectra observed for this helical peptide bear no resemblance to the spectra of α- or 310-helices and that while the FTIR spectra appear similar to spectra of β-sheets, 2D IR reveals that the observed resonances arise from vibrational modes unlike those observed in β-sheets. We also present an idealized model which reproduces the experimental data with high fidelity. This model is able to explain the polarization-dependence of the experimental 2D IR data. Using this model, we show the coupling between the rungs of the helix dominates the spectra, and as a consequence of this, the number of residues per turn can greatly influence the amide I spectra of gramicidin D.

| S-EPMC4401804 | biostudies-literature

Simulation study of chiral two-dimensional ultraviolet spectroscopy of the protein backbone.

Project description:Amide n-pi* and pi-pi* excitations around 200 nm are prominent spectroscopic signatures of the protein backbone, which are routinely used in ultraviolet (UV) circular dichroism for structure characterization. Recently developed ultrafast laser sources may be used to extend these studies to two dimensions. We apply a new algorithm for modeling protein electronic transitions to simulate two-dimensional UV photon echo signals in this regime and to identify signatures of protein backbone secondary (and tertiary) structure. Simulated signals for a set of globular and fibrillar proteins and their specific regions reveal characteristic patterns of helical and sheet secondary structures. We investigate how these patterns vary and converge with the size of the structural motif. Specific chiral polarization configurations of the UV pulses are found to be sensitive to aspects of the protein structure. This information significantly augments that available from linear circular dichroism.

| S-EPMC2896252 | biostudies-literature

Amyloid found in human cataracts with two-dimensional infrared spectroscopy.

Project description:UV light and other factors damage crystallin proteins in the eye lens, resulting in cataracts that scatter light and affect vision. Little information exists about protein structures within these disease-causing aggregates. We examined postmortem lens tissue from individuals with and without cataracts using 2D infrared (2DIR) spectroscopy. Amyloid β-sheet secondary structure was detected in cataract lenses along with denatured structures. No amyloid structures were found in lenses from juveniles, but mature lenses with no cataract diagnosis also contained amyloid, indicating that amyloid structures begin forming before diagnosis. Light scatters more strongly in regions with amyloid structure, and UV light induces amyloid β-sheet structures, linking the presence of amyloid structures to disease pathology. Establishing that age-related cataracts involve amyloid structures gives molecular insight into a common human affliction and provides a possible structural target for pharmaceuticals as an alternative to surgery.

| S-EPMC6452718 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data