Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid β Pathogenicity (2007)
Leila M. Luheshi, Gian Gaetano Tartaglia, Ann-Christin Brorsson, Amol P. Pawar, Ian E. Watson, Fabrizio Chiti, ...
Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases. We have established, using a computational approach,...
Importance of Metastable States in the Free Energy Landscapes of Polypeptide Chains (2007)
Auer, Stefan, Miller, Mark A., Krivov, Sergei V., Dobson, Christopher M., Karplus, Martin, Vendruscolo, Michele
We show that the interplay between excluded volume effects, hydrophobicity, and hydrogen bonding of a tube-like representation of a polypeptide chain gives rise to free energy landscapes that exhibit...
Mookyung Cheon, Iksoo Chang, Sandipan Mohanty, Leila M. Luheshi, Christopher M. Dobson, Michele Vendruscolo, ...
Increasing evidence indicates that oligomeric protein assemblies may represent the molecular species responsible for cytotoxicity in a range of neurological disorders including Alzheimer and...
Meehan, Sarah, Knowles, Tuomas P. J., Baldwin, Andrew J., Smith, Jeffrey F., Squires, Adam M., Clements, Philip Royston, ...
Copyright © 2007 Elsevier Ltd All rights reserved.
Yerbury, Justin J., Poon, Stephen, Meehan, Sarah, Thompson, Brianna, Kumita, Janet R., Dobson, Christopher M., ...
Copyright © 2007 by The Federation of American Societies for Experimental Biology.
Meehan, Sarah, Knowles, Tuomas P. J., Baldwin, Andrew J., Smith, Jeffrey F., Squires, Adam M., Clements, Philip Royston, ...
αB-Crystallin is a ubiquitous small heat-shock protein (sHsp) renowned for its chaperone ability to prevent target protein aggregation. It is stress-inducible and its up-regulation is associated...
Yerbury, Justin J., Poon, Stephen, Meehan, Sarah, Thompson, Brianna, Kumita, Janet R., Dobson, Christopher M., ...
Copyright © 2007 by The Federation of American Societies for Experimental Biology.
Selective removal of magnetization in coupled NMR spectra (2006)
Bodenhausen, Geoffrey, Dobson, Christopher M.
Two methods, based on the phase modulation of spin-echo signals due to J-coupling, of selective simplification of coupled homonuclear spectra are described. Both pulse methods employ a 90 Deg-t-180...
Heteronuclear NMR investigations of dynamic regions of intact Escherichia coli ribosomes (2004)
Christodoulou,John, Larsson,Göran, Fucini,Paola, Connell,Sean R., Pertinhez,Thelma A., Hanson,Charlotte L., ...
15N-1H NMR spectroscopy has been used to probe the dynamic properties of uniformly 15N labeled Escherichia coli ribosomes. Despite the high molecular weight of the complex ({approx}2.3 MDa), [1H-15N]...
Three-dimensional structures of translating ribosomes by Cryo-EM (2004)
Gilbert,Robert J. C., Fucini,Paola, Connell,Sean, Fuller,Stephen D., Nierhaus,Knud H., Robinson,Carol V., ...
Cryo-electron microscopy and image reconstruction techniques have been used to obtain three-dimensional maps for E. coli ribosomes stalled following translation of three representative proteins....
Three-dimensional structures of translating ribosomes by Cryo-EM (2004)
Gilbert, Robert J. C., Fucini, Paola, Connell, Sean, Fuller, Stephen D., Nierhaus, Knud H., Robinson, Carol V., ...
Cryo-electron microscopy and image reconstruction techniques have been used to obtain three-dimensional maps for E. coli ribosomes stalled following translation of three representative proteins....
Heteronuclear NMR investigations of dynamic regions of intact Escherichia coli ribosomes (2004)
Christodoulou, John, Larsson, Göran, Fucini, Paola, Connell, Sean R., Pertinhez, Thelma A., Hanson, Charlotte L., ...
15N-1H NMR spectroscopy has been used to probe the dynamic properties of uniformly 15N labeled Escherichia coli ribosomes. Despite the high molecular weight of the complex ({approx}2.3 MDa), [1H-15N]...
Robillard, George T., Scheek, Ruud M., Mateo, Pedro L., Duurkens, Ria, Titgemeijer, Fritz, Berends, Roel, ...
We have used site-directed mutagenesis in combination with a battery of biophysical techniques to probe the stability and folding behavior of a small globular protein, the histidine-containing...
Dobson, Christopher M., Robillard, George T., Scheek, Ruud M., Lyon, Charles E., Canet, Denis, Hore, Peter J., ...
We report the combined use of real-time photo-CIDNP NMR and stopped-flow fluorescence techniques to study the kinetic refolding of a set of mutants of a small globular protein, HPr, in which each of...
Slow Cooperative Folding of a Small Globular Protein HPr (1998)
Robillard, George T., Scheek, Ruud M., Forge, Vincent, Warner, Jessica, Meijberg, Wim, ...
The folding of an 85-residue protein, the histidine-containing phosphocarrier protein HPr, has been studied using a variety of techniques including DSC, CD, ANS fluorescence, and NMR spectroscopy. In...
Atmospheric aerosols as prebiotic chemical reactors
Dobson, Christopher M., Ellison, G. Barney, Tuck, Adrian F., Vaida, Veronica
Aerosol particles in the atmosphere have recently been found to contain a large number of chemical elements and a high content of organic material. The latter property is explicable by an inverted...
Fändrich, Marcus, Tito, Mark A., Leroux, Michel R., Rostom, Adam A., Hartl, F. Ulrich, Dobson, Christopher M., ...
We have analyzed a newly described archaeal GimC/prefoldin homologue, termed MtGimC, by using nanoflow electrospray coupled with time-of-flight MS. The molecular weight of the complex from...
Designing conditions for in vitro formation of amyloid protofilaments and fibrils
Chiti, Fabrizio, Webster, Paul, Taddei, Niccolò, Clark, Anne, Stefani, Massimo, Ramponi, Giampietro, ...
We have been able to convert a small α/β protein, acylphosphatase, from its soluble and native form into insoluble amyloid fibrils of the type observed in a range of pathological conditions. This...
Amyloid fibril formation by an SH3 domain
Guijarro, J. Iñaki, Sunde, Margaret, Jones, Jonathan A., Campbell, Iain D., Dobson, Christopher M.
The SH3 domain is a well characterized small protein module with a simple fold found in many proteins. At acid pH, the SH3 domain (PI3-SH3) of the p85α subunit of bovine phosphatidylinositol...
Mass spectrometry of ribosomes and ribosomal subunits
Benjamin, Dennis R., Robinson, Carol V., Hendrick, Joseph P., Hartl, F. Ulrich, Dobson, Christopher M.
Nanoflow electrospray ionization has been used to introduce intact Escherichia coli ribosomes into the ion source of a mass spectrometer. Mass spectra of remarkable quality result from a partial, but...
Detection of residue contacts in a protein folding intermediate
Balbach, Jochen, Forge, Vincent, Lau, Wai Shun, Jones, Jonathan A., Dobson, Christopher M.
Protein folding can be described in terms of the development of specific contacts between residues as a highly disordered polypeptide chain converts into the native state. Here we describe an NMR...
Detection and selective dissociation of intact ribosomes in a mass spectrometer
Rostom, Adam A., Fucini, Paola, Benjamin, Dennis R., Juenemann, Ralf, Nierhaus, Knud H., Hartl, F. Ulrich, ...
Intact Escherichia coli ribosomes have been projected into the gas phase of a mass spectrometer by means of nanoflow electrospray techniques. Species with mass/charge ratios in excess of 20,000 were...
The protofilament structure of insulin amyloid fibrils
Jiménez, José L., Nettleton, Ewan J., Bouchard, Mario, Robinson, Carol V., Dobson, Christopher M., Saibil, Helen R.
Under solution conditions where the native state is destabilized, the largely helical polypeptide hormone insulin readily aggregates to form amyloid fibrils with a characteristic cross-β structure....
The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation
Fändrich, Marcus, Dobson, Christopher M.
Amyloid fibrils and prions are proteinaceous aggregates that are based on a unique form of polypeptide configuration, termed cross-β structure. Using a group of chemically distinct polyamino acids,...
Altered aggregation properties of mutant γ-crystallins cause inherited cataract
Sandilands, Aileen, Hutcheson, Aileen M., Long, Heather A., Prescott, Alan R., Vrensen, Gijs, Löster, Jana, ...
Protein inclusions are associated with a diverse group of human diseases ranging from localized neurological disorders through to systemic non-neuropathic diseases. Here, we present evidence that the...
De novo designed peptide-based amyloid fibrils
Goldie, Kenneth, Zurdo, Jesús, Lacroix, Emmanuel, Dobson, Christopher M., Hoenger, Andreas, ...
Identification of therapeutic strategies to prevent or cure diseases associated with amyloid fibril deposition in tissue (Alzheimer's disease, spongiform encephalopathies, etc.) requires a rational...
Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril
Jaroniec, Christopher P., MacPhee, Cait E., Astrof, Nathan S., Dobson, Christopher M., Griffin, Robert G.
The molecular conformation of peptide fragment 105–115 of transthyretin, TTR(105–115), previously shown to form amyloid fibrils in vitro, has been determined by magic-angle spinning solid-state...
Chiti, Fabrizio, Calamai, Martino, Taddei, Niccolò, Stefani, Massimo, Ramponi, Giampietro, Dobson, Christopher M.
Protein aggregation and the formation of highly insoluble amyloid structures is associated with a range of debilitating human conditions, which include Alzheimer's disease, Parkinson's disease, and...
Structures and relative free energies of partially folded states of proteins
Vendruscolo, Michele, Paci, Emanuele, Karplus, Martin, Dobson, Christopher M.
The ability of proteins to fold to well defined compact structures is one of the most remarkable examples of the effect of natural selection on biological molecules. To understand their properties,...
Van Den Berg, Bert, Wain, Rachel, Dobson, Christopher M., Ellis, R.John
We have studied the effects of macromolecular crowding on protein folding kinetics by studying the oxidative refolding of hen lysozyme in the absence and presence of high concentrations of bovine...
Myoglobin forms amyloid fibrils by association of unfolded polypeptide segments
Fändrich, Marcus, Forge, Vincent, Buder, Katrin, Kittler, Marlis, Dobson, Christopher M., Diekmann, Stephan
Observations that β-sheet proteins form amyloid fibrils under at least partially denaturing conditions has raised questions as to whether these fibrils assemble by docking of preformed β-structure...
Mutational analysis of the propensity for amyloid formation by a globular protein
Chiti, Fabrizio, Taddei, Niccolò, Bucciantini, Monica, White, Paul, Ramponi, Giampietro, Dobson, Christopher M.
Acylphosphatase can be converted in vitro, by addition of trifluoroethanol (TFE), into amyloid fibrils of the type observed in a range of human diseases. The propensity to form fibrils has been...
Jaroniec, Christopher P., MacPhee, Cait E., Bajaj, Vikram S., McMahon, Michael T., Dobson, Christopher M., Griffin, Robert G.
Amyloid fibrils are self-assembled filamentous structures associated with protein deposition conditions including Alzheimer's disease and the transmissible spongiform encephalopathies. Despite the...
Exploring amyloid formation by a de novo design
Kammerer, Richard A., Kostrewa, Dirk, Zurdo, Jesús, Detken, Andreas, García-Echeverría, Carlos, Green, Janelle D., ...
Protein deposition as amyloid fibrils underlies many debilitating human disorders. The complexity and size of disease-related polypeptides, however, often hinders a detailed rational approach to...
Ventura, Salvador, Zurdo, Jesús, Narayanan, Saravanakumar, Parreño, Matilde, Mangues, Ramón, Reif, Bernd, ...
Protein misfolding and deposition underlie an increasing number of debilitating human disorders. We have shown that model proteins unrelated to disease, such as the Src homology 3 (SH3) domain of the...
Heteronuclear NMR investigations of dynamic regions of intact Escherichia coli ribosomes
Christodoulou, John, Larsson, Göran, Fucini, Paola, Connell, Sean R., Pertinhez, Thelma A., Hanson, Charlotte L., ...
15N-1H NMR spectroscopy has been used to probe the dynamic properties of uniformly 15N labeled Escherichia coli ribosomes. Despite the high molecular weight of the complex (≈2.3 MDa), [1H-15N]...
The formation of spherulites by amyloid fibrils of bovine insulin
Krebs, Mark R. H., MacPhee, Cait E., Miller, Aline F., Dunlop, Iain E., Dobson, Christopher M., Donald, Athene M.
Bovine insulin has long been known to self-assemble in vitro into amyloid fibrils. We have observed a further higher-order self-association of the protein into spherical structures, with diameters...
Multiple subsets of side-chain packing in partially folded states of α-lactalbumins
Mok, K. Hun, Nagashima, Toshio, Day, Iain J., Hore, P. J., Dobson, Christopher M.
Photochemically induced dynamic nuclear polarization NMR pulse-labeling techniques have been used to obtain detailed information about side-chain surface accessibilities in the partially folded...
Rational design of aggregation-resistant bioactive peptides: Reengineering human calcitonin
Fowler, Susan B., Poon, Stephen, Muff, Roman, Chiti, Fabrizio, Dobson, Christopher M., Zurdo, Jesús
A high propensity to aggregate into intractable deposits is a common problem limiting the production and use of many peptides and proteins in a wide range of biotechnological and pharmaceutical...
Salvatella, Xavier, Dobson, Christopher M., Fersht, Alan R., Vendruscolo, Michele
The protein barnase folds from the denatured state into its native conformation via a high-energy intermediate. Using ΦI-values determined experimentally from single-point mutations as restraints in...
Taguchi, Jocelyn E., Heyes, Stephen J., Barford, David, Johnson, Louise N., Dobson, Christopher M.
31P cross-polarization/magic angle sample spinning nuclear magnetic resonance spectra have been obtained for pyridoxal 5′-phosphate (PLP) bound to glycogen phosphorylase b (GPb) in two different...
Calculation of Mutational Free Energy Changes in Transition States for Protein Folding
Lindorff-Larsen, Kresten, Paci, Emanuele, Serrano, Luis, Dobson, Christopher M., Vendruscolo, Michele
Recent advances in experimental and computational methods have made it possible to determine with considerable accuracy the structures whose formation is rate limiting for the folding of some small...
The Circularization of Amyloid Fibrils Formed by Apolipoprotein C-II
Hatters, Danny M., MacRaild, Christopher A., Daniels, Rob, Gosal, Walraj S., Thomson, Neil H., Jones, Jonathan A., ...
Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a “cross-β” x-ray diffraction pattern. Whereas the latter demonstrates that...
Amyloid Fibril Formation Can Proceed from Different Conformations of a Partially Unfolded Protein
Calamai, Martino, Chiti, Fabrizio, Dobson, Christopher M.
Protein misfolding and aggregation are interconnected processes involved in a wide variety of nonneuropathic, systemic, and neurodegenerative diseases. More generally, if mutations in sequence or...
Atmospheric aerosols as prebiotic chemical reactors
Dobson, Christopher M., Ellison, G. Barney, Tuck, Adrian F., Vaida, Veronica
Aerosol particles in the atmosphere have recently been found to contain a large number of chemical elements and a high content of organic material. The latter property is explicable by an inverted...
Fändrich, Marcus, Tito, Mark A., Leroux, Michel R., Rostom, Adam A., Hartl, F. Ulrich, Dobson, Christopher M., ...
We have analyzed a newly described archaeal GimC/prefoldin homologue, termed MtGimC, by using nanoflow electrospray coupled with time-of-flight MS. The molecular weight of the complex from...
Designing conditions for in vitro formation of amyloid protofilaments and fibrils
Chiti, Fabrizio, Webster, Paul, Taddei, Niccolò, Clark, Anne, Stefani, Massimo, Ramponi, Giampietro, ...
We have been able to convert a small α/β protein, acylphosphatase, from its soluble and native form into insoluble amyloid fibrils of the type observed in a range of pathological conditions. This...
Amyloid fibril formation by an SH3 domain
Guijarro, J. Iñaki, Sunde, Margaret, Jones, Jonathan A., Campbell, Iain D., Dobson, Christopher M.
The SH3 domain is a well characterized small protein module with a simple fold found in many proteins. At acid pH, the SH3 domain (PI3-SH3) of the p85α subunit of bovine phosphatidylinositol...
Mass spectrometry of ribosomes and ribosomal subunits
Benjamin, Dennis R., Robinson, Carol V., Hendrick, Joseph P., Hartl, F. Ulrich, Dobson, Christopher M.
Nanoflow electrospray ionization has been used to introduce intact Escherichia coli ribosomes into the ion source of a mass spectrometer. Mass spectra of remarkable quality result from a partial, but...
Detection of residue contacts in a protein folding intermediate
Balbach, Jochen, Forge, Vincent, Lau, Wai Shun, Jones, Jonathan A., Dobson, Christopher M.
Protein folding can be described in terms of the development of specific contacts between residues as a highly disordered polypeptide chain converts into the native state. Here we describe an NMR...
Detection and selective dissociation of intact ribosomes in a mass spectrometer
Rostom, Adam A., Fucini, Paola, Benjamin, Dennis R., Juenemann, Ralf, Nierhaus, Knud H., Hartl, F. Ulrich, ...
Intact Escherichia coli ribosomes have been projected into the gas phase of a mass spectrometer by means of nanoflow electrospray techniques. Species with mass/charge ratios in excess of 20,000 were...
The protofilament structure of insulin amyloid fibrils
Jiménez, José L., Nettleton, Ewan J., Bouchard, Mario, Robinson, Carol V., Dobson, Christopher M., Saibil, Helen R.
Under solution conditions where the native state is destabilized, the largely helical polypeptide hormone insulin readily aggregates to form amyloid fibrils with a characteristic cross-β structure....
The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation
Fändrich, Marcus, Dobson, Christopher M.
Amyloid fibrils and prions are proteinaceous aggregates that are based on a unique form of polypeptide configuration, termed cross-β structure. Using a group of chemically distinct polyamino acids,...
Altered aggregation properties of mutant γ-crystallins cause inherited cataract
Sandilands, Aileen, Hutcheson, Aileen M., Long, Heather A., Prescott, Alan R., Vrensen, Gijs, Löster, Jana, ...
Protein inclusions are associated with a diverse group of human diseases ranging from localized neurological disorders through to systemic non-neuropathic diseases. Here, we present evidence that the...
De novo designed peptide-based amyloid fibrils
Goldie, Kenneth, Zurdo, Jesús, Lacroix, Emmanuel, Dobson, Christopher M., Hoenger, Andreas, ...
Identification of therapeutic strategies to prevent or cure diseases associated with amyloid fibril deposition in tissue (Alzheimer's disease, spongiform encephalopathies, etc.) requires a rational...
Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril
Jaroniec, Christopher P., MacPhee, Cait E., Astrof, Nathan S., Dobson, Christopher M., Griffin, Robert G.
The molecular conformation of peptide fragment 105–115 of transthyretin, TTR(105–115), previously shown to form amyloid fibrils in vitro, has been determined by magic-angle spinning solid-state...
Chiti, Fabrizio, Calamai, Martino, Taddei, Niccolò, Stefani, Massimo, Ramponi, Giampietro, Dobson, Christopher M.
Protein aggregation and the formation of highly insoluble amyloid structures is associated with a range of debilitating human conditions, which include Alzheimer's disease, Parkinson's disease, and...
Structures and relative free energies of partially folded states of proteins
Vendruscolo, Michele, Paci, Emanuele, Karplus, Martin, Dobson, Christopher M.
The ability of proteins to fold to well defined compact structures is one of the most remarkable examples of the effect of natural selection on biological molecules. To understand their properties,...
Van Den Berg, Bert, Wain, Rachel, Dobson, Christopher M., Ellis, R.John
We have studied the effects of macromolecular crowding on protein folding kinetics by studying the oxidative refolding of hen lysozyme in the absence and presence of high concentrations of bovine...
Myoglobin forms amyloid fibrils by association of unfolded polypeptide segments
Fändrich, Marcus, Forge, Vincent, Buder, Katrin, Kittler, Marlis, Dobson, Christopher M., Diekmann, Stephan
Observations that β-sheet proteins form amyloid fibrils under at least partially denaturing conditions has raised questions as to whether these fibrils assemble by docking of preformed β-structure...