A cylinder-shaped double ribbon structure formed by an amyloid hairpin peptide derived from the β-sheet of murine PrP: An X-ray and molecular dynamics simulation study

Croixmarie, Vincent; Briki, Fatma; David, Gabriel; Coïc, Yves-Marie; Ovtracht, L; Doucet, J.; Jamin, Nadège; Sanson, Alain

doi:10.1016/j.jsb.2005.03.003

Cited by 10 publications

(16 citation statements)

References 51 publications

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“…From the angular width of this arc, the coherent length of the core-b fibrils can be estimated at~85 Å . This value is of the same order as various amyloid fibers (10). In the smallangle x-ray scattering (SAXS) region, no particular signal is detectable; we find only a large diffuse halo.…”

Section: Histological Aspect Of Renal Aa Amyloidosissupporting

confidence: 61%

“…Therefore, a characterization of the folded structure within the fibers is necessary to achieve an unambiguous demonstration of the cross-b structure and the amyloid nature of the deposits. At the molecular scale, using a combination of data from various in vitro experiments and molecular simulation procedures, many sophisticated structure models were built (9,10). Spectroscopic analyses, such as circular dichroism or infrared spectroscopy of fibrils, generated in vitro or extracted from tissues all lead to the same conclusion about the high b-sheet content of the fibrils.…”

Section: Introductionmentioning

confidence: 99%

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Synchrotron X-Ray Microdiffraction Reveals Intrinsic Structural Features of Amyloid Deposits In Situ

Briki

Verine

Doucet

et al. 2011

Biophysical Journal

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Amyloidoses are increasingly recognized as a major public health concern in Western countries. All amyloidoses share common morphological, structural, and tinctorial properties. These consist of staining by specific dyes, a fibrillar aspect in electron microscopy and a typical cross-β folding in x-ray diffraction patterns. Most studies that aim at deciphering the amyloid structure rely on fibers generated in vitro or extracted from tissues using protocols that may modify their intrinsic structure. Therefore, the fine details of the in situ architecture of the deposits remain unknown. Here, we present to our knowledge the first data obtained on ex vivo human renal tissue sections using x-ray microdiffraction. The typical cross-β features from fixed paraffin-embedded samples are similar to those formed in vitro or extracted from tissues. Moreover, the fiber orientation maps obtained across glomerular sections reveal an intrinsic texture that is correlated with the glomerulus morphology. These results are of the highest importance to understanding the formation of amyloid deposits and are thus expected to trigger new incentives for tissue investigation. Moreover, the access to intrinsic structural parameters such as fiber size and orientation using synchrotron x-ray microdiffraction, could provide valuable information concerning in situ mechanisms and deposit formation with potential benefits for diagnostic and therapeutic purposes.

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Section: Histological Aspect Of Renal Aa Amyloidosissupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Synchrotron X-Ray Microdiffraction Reveals Intrinsic Structural Features of Amyloid Deposits In Situ

Briki

Verine

Doucet

et al. 2011

Biophysical Journal

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“…The electron and X‐ray diffraction data from filaments of Ure2p demonstrated the 4.7 Å reflection that is typical for the cross‐beta structure and highly indicative of amyloid [Baxa et al, 2005]. A structural model of the murine PrP small β‐sheet was obtained by the analysis of the 19‐mer comprising the two β‐strands 127–133 and 159–164 linked by a four‐residue sequence with high turn propensity [Croixmarie et al, 2005]. According to EM, this 19‐residue peptide spontaneously forms very long single fibrils.…”

Section: Protein Misfolding and Diseasesmentioning

confidence: 99%

“…Furthermore, the structure consists of two β‐sheet ribbons wound around a cylinder and assembled into a single fibril with a hairpin orientation perpendicular to the fibril axis. Molecular dynamics simulations revealed the zipper‐like network of polar interactions between the edges of the two ribbons, including the partially buried water molecules [Croixmarie et al, 2005]. High resolution X‐ray‐crystallographic data were used to determine the atomic structure of the cross‐beta spine from microcrystals formed by a seven‐residue peptide segment [Nelson et al, 2005].…”

Section: Protein Misfolding and Diseasesmentioning

confidence: 99%

Nanoimaging for protein misfolding and related diseases

Lyubchenko

Sherman

Shlyakhtenko

et al. 2006

J of Cellular Biochemistry

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Misfolding and aggregation of proteins is a common thread linking a number of important human health problems. The misfolded and aggregated proteins are inducers of cellular stress and activators of immunity in neurodegenerative diseases. They might possess clear cytotoxic properties, being responsible for the dysfunction and loss of cells in the affected organs. Despite the crucial importance of protein misfolding and abnormal interactions, very little is currently known about the molecular mechanism underlying these processes. Factors that lead to protein misfolding and aggregation in vitro are poorly understood, not to mention the complexities involved in the formation of protein nanoparticles with different morphologies (e.g., the nanopores) in vivo. A better understanding of the molecular mechanisms of misfolding and aggregation might facilitate development of the rational approaches to prevent pathologies mediated by protein misfolding. The conventional tools currently available to researchers can only provide an averaged picture of a living system, whereas much of the subtle or short-lived information is lost. We believe that the existing and emerging nanotools might help solving these problems by opening the entirely novel pathways for the development of early diagnostic and therapeutic approaches. This article summarizes recent advances of the nanoscience in detection and characterization of misfolded protein conformations. Based on these findings, we outline our view on the nanoscience development towards identification intracellular nanomachines and/or multicomponent complexes critically involved in protein misfolding.

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“…Remarkably, the strand-loop-strand conformation is shared by many other peptides in their fibrillar states, for example the Alzheimer's Ab(1-40) (11) and Ab(1-42) peptides (12), the HET-s fragment (13), the second WW domain of human CA150 transcriptional activator (14), and a 19-residue fragment of the murine prion protein (15). This observation raises the possibility that the strand-loop-strand could be a marginally populated structure in solution, acting as an aggregationprone building block for fibril assembly.…”

Section: Introductionmentioning

confidence: 99%

The β-Strand-Loop-β-Strand Conformation Is Marginally Populated in β2-Microglobulin (20–41) Peptide in Solution as Revealed by Replica Exchange Molecular Dynamics Simulations

Liang

Derreumaux

Mousseau

et al. 2008

Biophysical Journal

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Solid-state NMR study shows that the 22-residue K3 peptide (Ser(20)-Lys(41)) from beta(2)-microglobulin (beta(2)m) adopts a beta-strand-loop-beta-strand conformation in its fibril state. Residue Pro(32) has a trans conformation in the fibril state of the peptide, while it adopts a cis conformation in the native state of full-length beta(2)m. To get insights into the structural properties of the K3 peptide, and determine whether the strand-loop-strand conformation is encoded at the monomeric level, we run all-atom explicit solvent replica exchange molecular dynamics on both the cis and trans variants. Our simulations show that the conformational space of the trans- and cis-K3 peptides is very different, with 1% of the sampled conformations in common at room temperature. In addition, both variants display only 0.3-0.5% of the conformations with beta-strand-loop-beta-strand character. This finding, compared to results on the Alzheimer's Abeta peptide, suggests that the biases toward aggregation leading to the beta-strand-loop-beta-strand conformation in fibrils are peptide-dependent.

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A cylinder-shaped double ribbon structure formed by an amyloid hairpin peptide derived from the β-sheet of murine PrP: An X-ray and molecular dynamics simulation study

Cited by 10 publications

References 51 publications

Synchrotron X-Ray Microdiffraction Reveals Intrinsic Structural Features of Amyloid Deposits In Situ

Synchrotron X-Ray Microdiffraction Reveals Intrinsic Structural Features of Amyloid Deposits In Situ

Nanoimaging for protein misfolding and related diseases

The β-Strand-Loop-β-Strand Conformation Is Marginally Populated in β2-Microglobulin (20–41) Peptide in Solution as Revealed by Replica Exchange Molecular Dynamics Simulations

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