Amyloid fibril formation by a helical cytochrome

Pertinhez, Thelma A.; Bouchard, Mario; Tomlinson, Esther J.; Wain, Rachel; Ferguson, Stuart J.; Dobson, Christopher M.; Smith, Lorna J.

doi:10.1016/s0014-5793(01)02384-5

Cited by 123 publications

(131 citation statements)

References 19 publications

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“…NMR, nuclear magnetic resonance; Aβ, β-amyloid peptide; Ure2p 10-39 , residues 10-39 of the Ure2p yeast prion protein; EM, electron microscopy; FMOC, 9-fluorenylmethoxycarbonyl; TFA, trifluoroacetic acid; AFM, atomic force microscopy; MAS, magic-angle spinning; fpRFDR-CT, constant-time finite-pulse radiofrequency-driven recoupling; REDOR, rotational echo double resonance; DSQ, double single-quantum; TPPM, two-pulse phase modulation; CSA, chemical shift anisotropy; MD, molecular dynamics One goal of current efforts to elucidate the molecular structures of amyloid fibrils (1-35) is to identify the intermolecular interactions that determine the details of these structures and make amyloid fibrils a stable structural state for many peptides and proteins despite their diversity of amino acid sequences (36)(37)(38)(39)(40)(41). Recent studies by solid state nuclear magnetic resonance (NMR) of fibrils formed by the β-amyloid (Aβ) peptide associated with Alzheimer's disease (5,13,16,18,24,30,31), by various Aβ fragments (1,3,4,(6)(7)(8)12,21,25), and by other amyloidforming peptides (22) indicate that the β-sheets in amyloid fibrils have structures that tend to maximize contacts among hydrophobic residues when the component peptides contain continuous hydrophobic segments.…”

Section: Abbreviationsmentioning

confidence: 99%

Parallel β-Sheets and Polar Zippers in Amyloid Fibrils Formed by Residues 10−39 of the Yeast Prion Protein Ure2p

et al. 2005

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We report the results of solid state nuclear magnetic resonance (NMR) and atomic force microscopy measurements on amyloid fibrils formed by residues 10-39 of the yeast prion protein Ure2p (Ure2p ). Measurements of intermolecular 13 C-13 C nuclear magnetic dipole-dipole couplings indicate that Ure2p 10-39 fibrils contain in-register parallel β-sheets. Measurements of intermolecular 15 N-13 C dipole-dipole couplings, using a new solid state NMR technique called DSQ-REDOR, are consistent with hydrogen bonds between sidechain amide groups of Gln18 residues. Such sidechain hydrogen bonding interactions have been called "polar zippers" by M.F. Perutz and have been proposed to stabilize amyloid fibrils formed by peptides with glutamine-and asparaginerich sequences, such as Ure2p . We propose that polar zipper interactions account for the inregister parallel β-sheet structure in Ure2p 10-39 fibrils and that similar peptides will also exhibit parallel β-sheet structures in amyloid fibrils. We present molecular models for Ure2p fibrils that are consistent with available experimental data. Finally, we show that solid state 13 C NMR chemical shifts for 13 C-labeled Ure2p 10-39 fibrils are insensitive to hydration level, indicating that the fibril structure is not affected by the presence or absence of bulk water. AbbreviationsNMR, nuclear magnetic resonance; Aβ, β-amyloid peptide; Ure2p 10-39 , residues 10-39 of the Ure2p yeast prion protein; EM, electron microscopy; FMOC, 9-fluorenylmethoxycarbonyl; TFA, trifluoroacetic acid; AFM, atomic force microscopy; MAS, magic-angle spinning; fpRFDR-CT, constant-time finite-pulse radiofrequency-driven recoupling; REDOR, rotational echo double resonance; DSQ, double single-quantum; TPPM, two-pulse phase modulation; CSA, chemical shift anisotropy; MD, molecular dynamics One goal of current efforts to elucidate the molecular structures of amyloid fibrils (1-35) is to identify the intermolecular interactions that determine the details of these structures and make amyloid fibrils a stable structural state for many peptides and proteins despite their diversity of amino acid sequences (36)(37)(38)(39)(40)(41). Recent studies by solid state nuclear magnetic resonance (NMR) of fibrils formed by the β-amyloid (Aβ) peptide associated with Alzheimer's disease (5,13,16,18,24,30,31), by various Aβ fragments (1,3,4,(6)(7)(8)12,21,25), and by other amyloidforming peptides (22) indicate that the β-sheets in amyloid fibrils have structures that tend to maximize contacts among hydrophobic residues when the component peptides contain continuous hydrophobic segments. Electrostatic interactions appear to play a secondary role, dictating the choice between parallel and antiparallel β-sheet structures when either type of structure could maximize hydrophobic contacts (6,21,23) and dictating the precise registry of *corresponding author: Dr. Robert Tycko, National Institutes of Health, Building 5, Room 112, Bethesda, MD 20892-0520. phone 301-402-8272, fax 301-496-0825, e-mailrobertty@mail.nih -sh...

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Section: Abbreviationsmentioning

confidence: 99%

Parallel β-Sheets and Polar Zippers in Amyloid Fibrils Formed by Residues 10−39 of the Yeast Prion Protein Ure2p

et al. 2005

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“…There is increasing evidence that under appropriate conditions the amyloid state is accessible also to many other proteins that are not related to diseases, suggesting that the amyloid state is a generic structural feature, which might be adopted by any polypeptide chain (3)(4)(5)(6).…”

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Amyloid Features and Neuronal Toxicity of Mature Prion Fibrils Are Highly Sensitive to High Pressure

Moustaine

Perrier

et al. 2011

Journal of Biological Chemistry

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Prion proteins (PrP) can aggregate into toxic and possibly infectious amyloid fibrils. This particular macrostructure confers on them an extreme and still unexplained stability. To provide mechanistic insights into this self-assembly process, we used high pressure as a thermodynamic tool for perturbing the structure of mature amyloid fibrils that were prepared from recombinant full-length mouse PrP. Application of high pressure led to irreversible loss of several specific amyloid features, such as thioflavin T and 8-anilino-1-naphthalene sulfonate binding, alteration of the characteristic proteinase K digestion pattern, and a significant decrease in the ␤-sheet structure and cytotoxicity of amyloid fibrils. Partial disaggregation of the mature fibrils into monomeric soluble PrP was observed. The remaining amyloid fibrils underwent a change in secondary structure that led to morphologically different fibrils composed of a reduced number of proto-filaments. The kinetics of these reactions was studied by recording the pressure-induced dissociation of thioflavin T from the amyloid fibrils. Analysis of the pressure and temperature dependence of the relaxation rates revealed partly unstructured and hydrated kinetic transition states and highlighted the importance of collapsing and hydrating inter-and intramolecular cavities to overcome the high free energy barrier that stabilizes amyloid fibrils.Amyloid fibrils are filamentous polypeptide aggregates that are associated with devastating disorders such as Alzheimer and Parkinson diseases, type II diabetes, and prion (proteinaceous infectious particle) diseases, including Creutzfeldt-Jakob and mad cow disease (1, 2). There is increasing evidence that under appropriate conditions the amyloid state is accessible also to many other proteins that are not related to diseases, suggesting that the amyloid state is a generic structural feature, which might be adopted by any polypeptide chain (3-6).The development of in vitro model systems together with various biophysical and biochemical techniques (7-9) has improved the knowledge on the physicochemical basis of amyloid formation as well as on their structural and biochemical properties. It is now well recognized that a common property of amyloid fibrils is the extensive stacking of intermolecular ␤-strands that are arranged perpendicularly to the fibril axis and stabilized by a dense network of non-covalent interactions (10 -13). These fibrils consist of a variable number and arrangement of thin assemblies called proto-filaments that give rise to different fibril morphologies of diameters between 5 and 30 nanometers, both in in vitro preparations or in tissues (14 -22). Fibrils and their precursors are generally cytotoxic (23, 24) and are, thus, thought to be responsible for the neurodegeneration that is associated with many amyloid diseases.Yet the fundamental parameters that govern the protein aggregation process and dictate fibril stability/clearance are not well known. As the study of protein folding has been greatly advanc...

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“…Several non-pathogenic proteins and peptides also undergo amyloid like fibril formation on destabilization of their native state (7)(8)(9)(10). The fact that structurally and sequentially non-homologous proteins are able to self-assemble into fibrils possessing similar morphology (e.g.…”

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Early Events in the Fibrillation of Monomeric Insulin

Ahmad

Uversky

Hong

et al. 2005

Journal of Biological Chemistry

246

247

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Insulin has a largely ␣-helical structure and exists as a mixture of hexameric, dimeric, and monomeric states in solution, depending on the conditions: the protein is monomeric in 20% acetic acid. Insulin forms amyloid-like fibrils under a variety of conditions, especially at low pH. In this study we investigated the fibrillation of monomeric human insulin by monitoring changes in CD, attenuated total reflectance-Fourier transform infrared spectroscopy, 8-anilinonaphthalenesulfonic acid fluorescence, thioflavin T fluorescence, dynamic light scattering, and H/D exchange during the initial stages of the fibrillation process to provide insight into early events involving the monomer. The results demonstrate the existence of structural changes occurring before the onset of fibril formation, which are detectable by multiple probes. The data indicate at least two major populations of oligomeric intermediates between the native monomer and fibrils. Both have significantly non-native conformations, and indicate that fibrillation occurs from a betarich structure significantly distinct from the native fold.A number of human diseases are caused by the pathogenic deposition of proteins in the form of amyloid-like fibrils (1-7). Several non-pathogenic proteins and peptides also undergo amyloid like fibril formation on destabilization of their native state (7-10). The fact that structurally and sequentially non-homologous proteins are able to self-assemble into fibrils possessing similar morphology (e.g. 10 -18 nm width, birefringence to polarized light, and cross-␤ structure) suggests a common molecular mechanism in the fibrillation pathways. A variety of hypotheses for the mechanism of fibril formation have been proposed.Insulin is a 51-residue hormone with a largely ␣-helical structure. It exists as a mixture of hexameric, dimeric, and monomeric states in solution, with the relative population of different oligomeric species being strongly dependent on the environmental conditions: the protein is predominantly monomeric in 20% acetic acid, dimeric in 20 mM HCl, and hexameric at pH 7.5 in the presence of zinc. Insulin forms amyloidlike fibrils under a variety of conditions (11-13), with various overall morphologies depending on the arrangement of constituent protofilaments (14, 15). Insulin fibrils pose a variety of problems in biomedical and biotechnological applications. Amyloid deposits of insulin have been observed in patients with diabetes after repeated injection and in normal aging, as well as after subcutaneous insulin infusion (16,17).In our previous work we have shown the important role of partially folded intermediates in insulin fibrillation in vitro (13, 18 -20). In fact, our studies showed that insulin, which is a hexamer at physiological pH, undergoes rapid fibrillation starting at relatively low concentrations of guanidine hydrochloride and urea. The predominant species characterized by various biophysical techniques under these conditions was shown to be a partially folded, expanded monomer, which is presen...

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Amyloid fibril formation by a helical cytochrome

Cited by 123 publications

References 19 publications

Parallel β-Sheets and Polar Zippers in Amyloid Fibrils Formed by Residues 10−39 of the Yeast Prion Protein Ure2p

Parallel β-Sheets and Polar Zippers in Amyloid Fibrils Formed by Residues 10−39 of the Yeast Prion Protein Ure2p

Amyloid Features and Neuronal Toxicity of Mature Prion Fibrils Are Highly Sensitive to High Pressure

Early Events in the Fibrillation of Monomeric Insulin

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