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Full-Text Articles in Social and Behavioral Sciences
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 …
Enhanced Molecular Chaperone Activity Of The Small Heat-Shock Protein Alphab-Cystallin Following Covalent Immobilization Onto A Solid-Phase Support, V Bellotti, Heath Ecroyd, J Carver, H J Griesser, B Thierry, J G Shapter, S S Griesser, S Giorgetti, M R Nussio, J A Gerrard, J Garvey
Enhanced Molecular Chaperone Activity Of The Small Heat-Shock Protein Alphab-Cystallin Following Covalent Immobilization Onto A Solid-Phase Support, V Bellotti, Heath Ecroyd, J Carver, H J Griesser, B Thierry, J G Shapter, S S Griesser, S Giorgetti, M R Nussio, J A Gerrard, J Garvey
Heath Ecroyd
The well-characterized small heat-shock protein, alphaB-crystallin, acts as a molecular chaperone by interacting with unfolding proteins to prevent their aggregation and precipitation. Structural perturbation (e.g., partial unfolding) enhances the in vitro chaperone activity of alphaB-crystallin. Proteins often undergo structural perturbations at the surface of a synthetic material, which may alter their biological activity. This study investigated the activity of alphaB-crystallin when covalently bound to a support surface; alphaB-crystallin was immobilized onto a range of solid material surfaces, and its characteristics and chaperone activity were assessed. Immobilization was achieved via a plasma-deposited thin polymeric interlayer containing aldehyde surface groups and reductive …
The Interaction Of Unfolding Α-Lactalbumin And Malate Dehydrogenase With The Molecular Chaperone Αb-Crystallin: A Light And X-Ray Scattering Investigation, J W. Regini, Heath Ecroyd, Sarah Meehan, Kristen Bremmell, Matthew J. Clarke, Donna Lammie, Tim Wess, John A. Carver
The Interaction Of Unfolding Α-Lactalbumin And Malate Dehydrogenase With The Molecular Chaperone Αb-Crystallin: A Light And X-Ray Scattering Investigation, J W. Regini, Heath Ecroyd, Sarah Meehan, Kristen Bremmell, Matthew J. Clarke, Donna Lammie, Tim Wess, John A. Carver
Heath Ecroyd
Purpose: The molecular chaperone αB-crystallin is found in high concentrations in the lens and is present in all major body tissues. Its structure and the mechanism by which it protects its target protein from aggregating and precipitating are not known. Methods: Dynamic light scattering and X-ray solution scattering techniques were used to investigate structural features of the αB-crystallin oligomer when complexed with target proteins under mild stress conditions, i.e., reduction of α- lactalbumin at 37 °C and malate dehydrogenase when heated at 42 °C. In this investigation, the size, shape and particle distribution of the complexes were determined in real-time …
The Epididymal Soluble Prion Protein Forms A High-Molecular-Mass Complex In Association With Hydrophobic Proteins, Heath W. Ecroyd, Maya Belghazi, Jean-Louis Dacheux, Jean-Luc Gatti
The Epididymal Soluble Prion Protein Forms A High-Molecular-Mass Complex In Association With Hydrophobic Proteins, Heath W. Ecroyd, Maya Belghazi, Jean-Louis Dacheux, Jean-Luc Gatti
Heath Ecroyd
We have shown previously that a 'soluble' form of PrP (prion protein), not associated with membranous vesicles, exists in the male reproductive fluid [Ecroyd, Sarradin, Dacheux and Gatti (2004) Biol. Reprod. 71, 993-1001]. Attempts to purify this 'soluble' PrP indicated that it behaves like a high-molecular-mass complex of more than 350 kDa and always co-purified with the same set of proteins. The main associated proteins were sequenced by MS and were found to match to clusterin (apolipoprotein J), BPI (bacterial permeability-increasing protein), carboxylesterase-like urinary excreted protein (cauxin), beta-mannosidase and beta-galactosidase. Immunoblotting and enzymatic assay confirmed the presence of clusterin and …