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Full-Text Articles in Physical Sciences and Mathematics
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 …
The Small Heat-Shock Proteins Hspb2 And Hspb3 Form Well-Defined Heterooligomers In A Unique 3 To 1 Subunit Ratio, J. Den Engelsman, S. Baros, P. Y. W. Dankers, B. Kamps, W. T. Vree Egberts, C. S. Bode, L. A. Lane, J. A. Aquilina, J. L. P. Benesch, C. V. Robinson, W. W. De Jong, W. C. Boelens
The Small Heat-Shock Proteins Hspb2 And Hspb3 Form Well-Defined Heterooligomers In A Unique 3 To 1 Subunit Ratio, J. Den Engelsman, S. Baros, P. Y. W. Dankers, B. Kamps, W. T. Vree Egberts, C. S. Bode, L. A. Lane, J. A. Aquilina, J. L. P. Benesch, C. V. Robinson, W. W. De Jong, W. C. Boelens
J. A. Aquilina
Various mammalian small heat-shock proteins (sHSPs) can interact with one another to form large polydisperse assemblies. In muscle cells, HSPB2/MKBP (myotonic dystrophy protein kinase-binding protein) and HSPB3 have been shown to form an independent complex. To date, the biochemical properties of this complex have not been thoroughly characterized. In this study, we show that recombinant HSPB2 and HSPB3 can be successfully purified from E.coli cells co-expressing both proteins. Nanoelectrospray ionization mass spectrometry and sedimentation velocity analytical ultracentrifugation analysis showed that HSPB2/B3 forms a series of well defined hetero-oligomers, consisting of 4, 8, 12, 16, 20 and 24 subunits, each maintaining …
Evidence For Specific Subunit Distribution And Interactions In The Quaternary Structure Of Α-Crystallin, Amie M. Morris, J Andrew Aquilina
Evidence For Specific Subunit Distribution And Interactions In The Quaternary Structure Of Α-Crystallin, Amie M. Morris, J Andrew Aquilina
J. A. Aquilina
The quaternary structure of alpha-crystallin is dynamic, a property which has thwarted crystallographic efforts towards structural characterization. In this study, we have used collision-induced dissociation mass spectrometry to examine the architecture of the polydisperse assemblies of alpha-crystallin. For total alpha-crystallin isolated directly from fetal calf lens using size-based chromatography, the alpha B-crystallin subunit was found to be preferentially dissociated from the oligomers, despite being significantly less abundant overall than the alpha A-crystallin subunits. Furthermore, upon mixing molar equivalents of purified alpha A- and alpha B-crystallin, the levels of their dissociation were found to decrease and increase, respectively, with time. Interestingly …
Mimicking Phosphorylation Of Alphab-Crystallin Affects Its Chaperone Activity, Heath W. Ecroyd, Sarah Meehan, J Horwitz, Andrew Aquilina, J L Benesch, C V Robinson, Cait Macphee, John Carver
Mimicking Phosphorylation Of Alphab-Crystallin Affects Its Chaperone Activity, Heath W. Ecroyd, Sarah Meehan, J Horwitz, Andrew Aquilina, J L Benesch, C V Robinson, Cait Macphee, John Carver
J. A. Aquilina
No abstract provided.
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 …
Mimicking Phosphorylation Of Alphab-Crystallin Affects Its Chaperone Activity, Heath W. Ecroyd, Sarah Meehan, J Horwitz, Andrew Aquilina, J L Benesch, C V Robinson, Cait Macphee, John Carver
Mimicking Phosphorylation Of Alphab-Crystallin Affects Its Chaperone Activity, Heath W. Ecroyd, Sarah Meehan, J Horwitz, Andrew Aquilina, J L Benesch, C V Robinson, Cait Macphee, John Carver
Heath Ecroyd
No abstract provided.
Crystallin Proteins And Amyloid Fibrils, Heath Ecroyd, John A. Carver
Crystallin Proteins And Amyloid Fibrils, Heath Ecroyd, John A. Carver
Heath Ecroyd
Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, alpha-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of alpha B-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, …
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Heath Ecroyd
Amyloid fibril formation is associated with diseases such as Alzheimer’s, Parkinson’s, and prion diseases. Inhibition of amyloid fibril formation by molecular chaperone proteins, such as the small heat-shock protein αB-crystallin, may play a protective role in preventing the toxicity associated with this form of protein misfolding. Reduced and carboxymethylated κ-casein (RCMκ-CN), a protein derived from milk, readily and reproducibly forms fibrils at physiological temperature and pH. We investigated the toxicity of fibril formation by RCMκ-CN using neuronal model PC12 cells and determined whether the inhibition of fibril formation altered its cell toxicity. To resolve ambiguities in the literature, we also …
The Interaction Of Alphab-Crystallin With Mature Alpha-Synuclein Amyloid Fibrils Inhibits Their Elongation, Christopher A. Waudby, Tuomas P. J Knowles, Glyn L. Devlin, Jeremy N. Skepper, Heath Ecroyd, John A. Carver, Mark E. Welland, John Christodoulou, Christopher M. Dobson, Sarah Meehan
The Interaction Of Alphab-Crystallin With Mature Alpha-Synuclein Amyloid Fibrils Inhibits Their Elongation, Christopher A. Waudby, Tuomas P. J Knowles, Glyn L. Devlin, Jeremy N. Skepper, Heath Ecroyd, John A. Carver, Mark E. Welland, John Christodoulou, Christopher M. Dobson, Sarah Meehan
Heath Ecroyd
alphaB-Crystallin is a small heat-shock protein (sHsp) that is colocalized with alpha-synuclein (alphaSyn) in Lewy bodies—the pathological hallmarks of Parkinson's disease—and is an inhibitor of alphaSyn amyloid fibril formation in an ATP-independent manner in vitro. We have investigated the mechanism underlying the inhibitory action of sHsps, and here we establish, by means of a variety of biophysical techniques including immunogold labeling and nuclear magnetic resonance spectroscopy, that alphaB-crystallin interacts with alphaSyn, binding along the length of mature amyloid fibrils. By measurement of seeded fibril elongation kinetics, both in solution and on a surface using a quartz crystal microbalance, this binding …