Dataset Information

Stability of A?-fibril fragments in the presence of fatty acids.

ABSTRACT: We consider the effect of lauric acid on the stability of various fibril-like assemblies of A? peptides. For this purpose, we have performed molecular dynamics simulations of these assemblies either in complex with lauric acid or without presence of the ligand. While we do not observe a stabilizing effect on A?40 -fibrils, we find that addition of lauric acid strengthens the stability of fibrils built from the triple-stranded S-shaped A?42 -peptides considered to be more toxic. Or results may help to understand how the specifics of the brain-environment modulate amyloid formation and propagation.

SUBMITTER: Xi W

PROVIDER: S-EPMC6798130 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Stability of Aβ-fibril fragments in the presence of fatty acids.

Xi Wenhui W Vanderford Elliott K EK Liao Qinxin Q Hansmann Ulrich H E UHE

Protein science : a publication of the Protein Society 20190911 11

We consider the effect of lauric acid on the stability of various fibril-like assemblies of Aβ peptides. For this purpose, we have performed molecular dynamics simulations of these assemblies either in complex with lauric acid or without presence of the ligand. While we do not observe a stabilizing effect on Aβ<sub>40</sub> -fibrils, we find that addition of lauric acid strengthens the stability of fibrils built from the triple-stranded S-shaped Aβ<sub>42</sub> -peptides considered to be more to ...[more]

PMID: 31461191

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Project description:Short peptide sequences within the microtubule binding domain of the protein Tau are proposed to be core nucleation sites for formation of amyloid fibrils displaying the paired helical filament (PHF) morphology characteristic of neurofibrillary tangles. To study the structure of these proposed nucleation sites, we analyzed the x-ray diffraction patterns from the assemblies formed by a variety of PHF/tau-related peptide constructs containing the motifs VQIINK (PHF6*) in the second repeat and VQIVYK (PHF6) in the third repeat of tau. Peptides included: tripeptide acetyl-VYK-amide (AcVYK), tetrapeptide acetyl-IVYK-amide (AcPHF4), hexapeptide acetyl-VQIVYK-amide (AcPHF6), and acetyl-GKVQIINKLDLSNVQKDNIKHGSVQIVYKPVDLSKVT-amide (AcTR4). All diffraction patterns showed reflections at spacings of 4.7 A, 3.8 A, and approximately 8-10 A, which are characteristic of an orthogonal unit cell of beta-sheets having dimensions a=9.4 A, b=6.6 A, and c=approximately 8-10 A (where a, b, and c are the lattice constants in the H-bonding, chain, and intersheet directions). The sharp 4.7 A reflections indicate that the beta-crystallites are likely to be elongated along the H-bonding direction and in a cross-beta conformation. The assembly of the AcTR4 peptide, which contains both the PHF6 and PHF6* motifs, consisted of twisted sheets, as indicated by a unique fanning of the diffuse equatorial scattering and meridional accentuation of the (210) reflection at 3.8 A spacing. The diffraction data for AcVYK, AcPHF4, and AcPHF6 all were consistent with approximately 50 A-wide tubular assemblies having double-walls, where beta-strands constitute the walls. In this structure, the peptides are H-bonded together in the fiber direction, and the intersheet direction is radial. The positive-charged lysine residues face the aqueous medium, and tyrosine-tyrosine aromatic interactions stabilize the intersheet (double-wall) layers. This particular contact, which may be involved in PHF fibril formation, is proposed here as a possible aromatic target for anti-tauopathy drugs.

Dataset Information

Stability of A?-fibril fragments in the presence of fatty acids.

Publications

Stability of Aβ-fibril fragments in the presence of fatty acids.

Similar Datasets

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