Probing aromatic, hydrophobic, and steric effects on the self-assembly of an amyloid-β fragment peptide

2011 ◽  
Vol 7 (2) ◽  
pp. 486-496 ◽  
Author(s):  
F. Timur Senguen ◽  
Naomi R. Lee ◽  
Xianfeng Gu ◽  
Derek M. Ryan ◽  
Todd M. Doran ◽  
...  
Keyword(s):  
Self Assembly ◽  
Amyloid Β ◽  
The Self ◽  
Steric Effects

scholarly journals An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Devkee M. Vadukul ◽  
Céline Vrancx ◽  
Pierre Burguet ◽  
Sabrina Contino ◽  
Nuria Suelves ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Self Assembly ◽  
Critical Nucleus ◽  
Amyloid Fibril ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
The Self ◽  
Aβ Peptide ◽  
Amyloid Fibril Formation ◽  
Secretase Activity

AbstractA key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers.

scholarly journals Reproducibility Problems of Amyloid-β Self-Assembly and How to Deal With Them

2021 ◽  
Vol 8 ◽  
Author(s):  
Peter Faller ◽  
Christelle Hureau
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Self Assembly ◽  
Amyloid Fibrils ◽  
Amyloid Β ◽  
Test Tube ◽  
The Self ◽  
Aggregation Process ◽  
Self Assembled

The self-assembly of peptides and proteins into amyloid fibrils and other aggregates are linked to several diseases. One of the most studied cases is the peptide amyloid-β (Aβ), found self-assembled in Alzheimer's disease patients' brains. In test tubes, assays with chemically synthesized or recombinant Aβ are widely investigated to understand the aggregation process and to find modulators, which could be of therapeutic interest. Experience over more than a decade in our laboratory through discussions with colleagues, expertly studying the literature, and as reviewers revealed to us the widely encountered difficulty to control the aggregation and obtain reproducible results in the test tube. However, this issue is scarcely reported and discussed in the publications, which we think hampers strongly the progress in this field and can deceive newcomers. Here, we describe the difficulty and potential reasons to obtain reproducible aggregation data and propose some guidelines for working with it.

Steric Effects in the Self-Assembly of Palladium Complexes with Chelating Diamine Ligands

2008 ◽  
Vol 2008 (10) ◽  
pp. 1573-1583 ◽  
Author(s):  
Eszter Holló-Sitkei ◽  
Gábor Tárkányi ◽  
László Párkányi ◽  
Tünde Megyes ◽  
Gábor Besenyei
Keyword(s):  
Self Assembly ◽  
Palladium Complexes ◽  
The Self ◽  
Steric Effects ◽  
Diamine Ligands

scholarly journals SAXS/WAXS Investigation of Amyloid-β(16-22) Peptide Nanotubes

2021 ◽  
Vol 9 ◽  
Author(s):  
Theyencheri Narayanan ◽  
Axel Rüter ◽  
Ulf Olsson
Keyword(s):  
Self Assembly ◽  
Amyloid Β ◽  
Structural Elucidation ◽  
The Self ◽  
Assembly Process ◽  
Peptide Nanotubes ◽  
Short Peptide ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

This brief report presents an X-ray scattering investigation of self-assembled nanotubes formed by a short peptide. X-ray scattering methods enable multiscale structural elucidation of these nanotubes in solution under the same conditions involved in the self-assembly process. In particular, the dimensions of nanotubes and the crystalline organization within their walls can be determined quantitatively. This is illustrated in the case of amyloid-β(16-22) peptide nanotubes.

Role of Metal Ions in the Self-assembly of the Alzheimer’s Amyloid-β Peptide

2013 ◽  
Vol 52 (21) ◽  
pp. 12193-12206 ◽  
Author(s):  
Peter Faller ◽  
Christelle Hureau ◽  
Olivia Berthoumieu
Keyword(s):  
Metal Ions ◽  
Self Assembly ◽  
Amyloid Β ◽  
The Self ◽  
Amyloid Β Peptide

Rosette Nanotubes: Factors Affecting the Self-assembly of the Monobases Versus the Twin Base System

2007 ◽  
Vol 1057 ◽  
Author(s):  
Usha Hemraz ◽  
Hicham Fenniri
Keyword(s):  
Self Assembly ◽  
The Self ◽  
Dna Bases ◽  
Steric Effects ◽  
Base System ◽  
Factors Affecting ◽  
Rosette Nanotubes

ABSTRACTRosette Nanotubes (RNTs) are formed by the self-assembly of a guanine-cytosine motif (GΛC), a hybrid of the DNA bases guanine and cytosine, to give a six membered macrocycle maintained by 18 H-bonds. In theory, any moiety covalently attached to the GΛC base can be expressed on the nanotubes surface. However we anticipate that the self-assembly and stability of these functionalised RNTs will also be governed by steric effects. Herein we describe the synthesis and the self assembly of the Twin Base Lysine (TBL-K) and its monobase (MBL-K). While TBL-K self-assembles readily in water and methanol to give nanotubular structures, MBL-K does not form nanotubes. Various techniques were used to characterize the RNTs and the factors, preventing self-assembly in the case of MBL-K, were investigated.

Sterically controlled self-assembly of tetrahedral M6L4cages via cationic N-donor ligands

2014 ◽  
Vol 50 (41) ◽  
pp. 5469-5472 ◽  
Author(s):  
Anssi Peuronen ◽  
Samu Forsblom ◽  
Manu Lahtinen
Keyword(s):  
Self Assembly ◽  
The Self ◽  
Donor Ligands ◽  
Steric Effects

Inter-ligand steric effects dictate the self-assembly between tripodal cationic ligandLand MII(M = Cu, Pd) generating an unusual tetrahedral M6L4cage instead of the expected M6L8species.

scholarly journals Interaction of Aβ42 with Membranes Triggers the Self-Assembly into Oligomers

2020 ◽  
Vol 21 (3) ◽  
pp. 1129 ◽  
Author(s):  
Siddhartha Banerjee ◽  
Mohtadin Hashemi ◽  
Karen Zagorski ◽  
Yuri L. Lyubchenko
Keyword(s):  
Self Assembly ◽  
Membrane Surface ◽  
Amyloid Β ◽  
The Self ◽  
Bulk Solution ◽  
Aggregation Process ◽  
Physiological Concentration ◽  
Dynamics Simulations

The self-assembly of amyloid β (Aβ) proteins into oligomers is the major pathogenic event leading to Alzheimer’s disease (AD). Typical in vitro experiments require high protein concentrations, whereas the physiological concentration of Aβ is in the picomolar to low nanomolar range. This complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here, we demonstrate that Aβ42 self-assembles into aggregates on membrane bilayers at low nanomolar concentrations - a pathway in which the membrane plays the role of a catalyst. Additionally, physiological ionic conditions (150 mM NaCl) significantly enhance on-membrane aggregation, leading to the rapid formation of oligomers. The self-assembly process is reversible, so assembled aggregates can dissociate from the membrane surface into the bulk solution to further participate in the aggregation process. Molecular dynamics simulations demonstrate that the transient membrane-Aβ interaction dramatically changes the protein conformation, facilitating the assembly of dimers. The results indicate peptide–membrane interaction is the critical step towards oligomer formation at physiologically low protein concentrations.

scholarly journals Unravelling the role of amino acid sequence order in the assembly and function of the amyloid-β core

2019 ◽  
Vol 55 (59) ◽  
pp. 8595-8598 ◽  
Author(s):  
Santu Bera ◽  
Elad Arad ◽  
Lee Schnaider ◽  
Shira Shaham-Niv ◽  
Valeria Castelletto ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Self Assembly ◽  
Amyloid Β ◽  
The Self ◽  
Biological Functions ◽  
The Core ◽  
Recognition Motif ◽  
And Function

Here we report the influence of amino acid sequence order on the self-assembly and biological functions of the core recognition motif of Amyloid β.

scholarly journals Spontaneous Self-assembly of Amyloid β (1-40) into Dimers

2019 ◽  
Author(s):  
Mohtadin Hashemi ◽  
Yuliang Zhang ◽  
Zhengjian Lv ◽  
Yuri L. Lyubchenko
Keyword(s):  
Molecular Dynamics ◽  
Self Assembly ◽  
Amyloid Β ◽  
Conformational Transitions ◽  
Terminal Region ◽  
The Self ◽  
Hydrophobic Region ◽  
Peptide Interactions ◽  
Long Time ◽  
Dynamics Simulations

AbstractThe self-assembly and fibrillation of amyloid β (Aβ) proteins is the neuropathological hallmark of Alzheimer’s disease. However, the molecular mechanism of how disordered monomers assemble into aggregates remains largely unknown. In this work, we characterize the assembly of Aβ (1-40) monomers into dimers using long-time molecular dynamics simulations. Upon interaction, the monomers undergo conformational transitions, accompanied by change of the structure, leading to the formation of a stable dimer. The dimers are primarily stabilized by interactions in the N-terminal region (residues 5-12), in the central hydrophobic region (residues 16-23), and in the C-terminal region (residues 30-40); with inter-peptide interactions focused around the N- and C- termini. The dimers do not contain long β-strands that are usually found in fibrils.

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