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Articles 1 - 3 of 3
Full-Text Articles in Social and Behavioral Sciences
The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver
The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver
Heath Ecroyd
The ability of small heat-shock proteins (sHsps) such as alphaB-crystallin to inhibit the amorphous (disordered) aggregation of varied target proteins in a chaperone-like manner has been well described. The mechanistic details of this action are not understood. Amyloid fibril formation is an alternative off-folding pathway that leads to highly ordered beta-sheet-containing aggregates. Amyloid fibril formation is associated with a broad range of protein conformational diseases such as Alzhiemer's, Parkinson's and Huntington's and sHsp expression is elevated in the protein deposits that are characteristic of these disease states. The ability of sHsps to prevent fibril formation has been less well characterised. …
Molecular Dynamics Analysis Of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism For Selective Oxidation Of Met-93, Aaron J. Oakley, Surabhi Bhatia, Heath Ecroyd, Brett Garner
Molecular Dynamics Analysis Of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism For Selective Oxidation Of Met-93, Aaron J. Oakley, Surabhi Bhatia, Heath Ecroyd, Brett Garner
Heath Ecroyd
Background: Recent studies suggest reduction of radical-propagating fatty acid hydroperoxides to inert hydroxides by interaction with apolipoprotein-D (apoD) Met93 may represent an antioxidant function for apoD. The nature and structural consequences of this selective interaction are unknown. Methodology/Principal Findings: Herein we used molecular dynamics (MD) analysis to address these issues. Longtimescale simulations of apoD suggest lipid molecules are bound flexibly, with the molecules free to explore multiple conformations in a binding site at the entrance to the classical lipocalin ligand-binding pocket. Models of 5s- 12s- and 15s hydroperoxyeicosatetraenoic acids were created and the lipids found to wrap around Met93 thus …
Binding Of The Molecular Chaperone Alphab-Crystallin To Abeta Amyloid Fibrils Inhibits Fibril Elongation, Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. Knowles, Heath W. Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, Sarah Meehan
Binding Of The Molecular Chaperone Alphab-Crystallin To Abeta Amyloid Fibrils Inhibits Fibril Elongation, Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. Knowles, Heath W. Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, Sarah Meehan
Heath Ecroyd
The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ42 fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ42. Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect …