Effects of lysine residues on structural characteristics and stability of tau proteins

Lee, Myeongsang; Baek, Inchul; Choi, Hyunsung; Kim, Jae In; Na, Sungsoo

doi:10.1016/j.bbrc.2015.09.056

Cited by 12 publications

(14 citation statements)

References 49 publications

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“…However,h eterogeneous buildingb locks showedr emarkably different binding energies between blocks (Figure 3d). [67,94] Structural deformations of amyloid blocks driven by ah igh degree of freedom weaken the interactions between inter-layersa nd create unclear binding site. In both heterogeneousa nd homogeneous blocks, the smaller the binding energy was computed, the highert he RMSF value was presented (Figure S9 ba nd Figure3e).…”

Section: Bindingenergies and Root Mean Squared Fluctuation (Rmsf)mentioning

confidence: 99%

Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules

et al. 2017

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In biological systems, structural confinements of amyloid fibrils can be mediated by the role of water molecules. However, the underlying effect of the dynamic behavior of water molecules on structural stabilities of amyloid fibrils is still unclear. By performing molecular dynamics simulations, we investigate the dynamic features and the effect of interior water molecules on conformations and mechanical characteristics of various amyloid fibrils. We find that a specific mechanism induced by the dynamic properties of interior water molecules can affect diffusion of water molecules inside amyloid fibrils, inducing their different structural stabilities. The conformation of amyloid fibrils induced by interior water molecules show the fibrils' different mechanical features. We elucidate the role of confined and movable interior water molecules in structural stabilities of various amyloid fibrils. Our results offer insights not only in further understanding of mechanical features of amyloids as mediated by water molecules, but also in the fine-tuning of the functional abilities of amyloid fibrils for applications.

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Section: Bindingenergies and Root Mean Squared Fluctuation (Rmsf)mentioning

confidence: 99%

Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules

et al. 2017

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“…revealed that the amyloid fibrillar growth mechanisms related to repetitive elongation and fragmentation and their growth mechanisms are related to cytotoxicity behaviors . In a similar manner, several computational groups hypothesized that as the oligomers elongate via aggregation, the structures become unstable and tend to fracture at a specific length and size . From their studies, suggested growth amyloid fibril pairs were formed by each fractured fibril, which are more stable than oligomer pairs.…”

Section: Resultsmentioning

confidence: 97%

“…Furthermore, not only does the RMSD value allude to the structural characteristics, but the twist angles also denote how much the amyloids (i.e. oligomer and fibrils) is changed from an equilibration simulation with respect to the conformation . Figure 3(b,d) shows the twist angle variation of the polymorphic F20L and WT Aβ pair oligomers with respect to time.…”

Section: Resultsmentioning

confidence: 99%

“…reported the specific size of Aβ 17‐42 amyloid oligomers that exhibit structural instability using geometric and binding energy analysis . Our previous study also revealed that the specific length of an amyloid oligomer is associated with stability, which can be related to fibrillar growth …”

Section: Introductionmentioning

confidence: 91%

“…Moreover, they determined the structural and biophysical properties of fragmented amyloid fibrils; short fragmented amyloid fibrils are more closely associated with cytotoxic properties than longer amyloids. Computational studies have been applied to a more detailed analysis of fragmented amyloid fibrils and oligomer structures . For example, Wu et al .…”

Section: Introductionmentioning

confidence: 99%

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Structural analysis of oligomeric and protofibrillar Aβ amyloid pair structures considering F20L mutation effects using molecular dynamics simulations

et al. 2017

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Aβ amyloid proteins are involved in neuro-degenerative diseases such as Alzheimer's, Parkinson's, and so forth. Because of its structurally stable feature under physiological conditions, Aβ amyloid protein disrupts the normal cell function. Because of these concerns, understanding the structural feature of Aβ amyloid protein in detail is crucial. There have been some efforts on lowering the structural stabilities of Aβ amyloid fibrils by decreasing the aromatic residues characteristic and hydrophobic effect. Yet, there is a lack of understanding of Aβ amyloid pair structures considering those effects. In this study, we provide the structural characteristics of wildtype (WT) and phenylalanine residue mutation to leucine (F20L) Aβ amyloid pair structures using molecular dynamics simulation in detail. We also considered the polymorphic feature of F20L and WT Aβ pair amyloids based on the facing β-strand directions between the amyloid pairs. As a result, we were able to observe the varying effects of mutation, polymorphism, and protofibril lengths on the structural stability of pair amyloids. Furthermore, we have also found that opposite structural stability exists on a certain polymorphic Aβ pair amyloids depending on its oligomeric or protofibrillar state, which can be helpful for understanding the amyloid growth mechanism via repetitive fragmentation and elongation mechanism. Proteins 2017; 85:580-592. © 2016 Wiley Periodicals, Inc.

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End Capping Alters the Structural Characteristics and Mechanical Properties of Transthyretin (105–115) Amyloid Protofibrils

Lee

2015

ChemPhysChem

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Pathological amyloid proteins are associated with degenerative and neurodegenerative diseases. These amyloid proteins develop as oligomer, fibrillar, and plaque forms, due to the denatured and unstable status of the amyloid monomers. Specifically, the development of fibrillar amyloid proteins has been investigated through several experimental studies. To understand the generation of amyloid fibrils, environmental factors such as point mutations, pH, and polymorphic characteristics have been considered. Recently, amyloid fibril studies related to end-capping effects have been conducted to understand amyloid fibril development. However, atomic-level studies to determine the stability and mechanical properties of amyloid fibrils based on end capping have not been undertaken. In this study, we show that end capping alters the structural characteristics and conformations of transthyretin (TTR) amyloid fibrils by using molecular dynamics (MD) simulations. Variation in the structural conformations and characteristics of the TTR fibrils through end capping are observed, due to the resulting electrostatic energies and hydrophobicity characteristics. Moreover, the end capping changes the mechanical properties of TTR fibrils. Our results shed light on amyloid fibril formation under end-capping conditions.

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Effects of lysine residues on structural characteristics and stability of tau proteins

Cited by 12 publications

References 49 publications

Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules

Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules

Structural analysis of oligomeric and protofibrillar Aβ amyloid pair structures considering F20L mutation effects using molecular dynamics simulations

End Capping Alters the Structural Characteristics and Mechanical Properties of Transthyretin (105–115) Amyloid Protofibrils

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