Bildung von Peptidfibrillen

Hamley, Ian W.

doi:10.1002/ange.200700861

Cited by 68 publications

(47 citation statements)

References 270 publications

(400 reference statements)

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“…The presence of a lag phase in the observed amyloid formation of PP and g10 indicates a nucleation-dependent polymerization pathway. [27] Nucleus formation is usually a rate-limiting step in amyloid formation. It is followed by a fast elongation phase, which results in mature amyloids.…”

Section: Peptidementioning

confidence: 99%

How Post‐Translational Modifications Influence Amyloid Formation: A Systematic Study of Phosphorylation and Glycosylation in Model Peptides

Broncel

Falenski

Wagner

et al. 2010

Chemistry A European J

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A reciprocal relationship between phosphorylation and O-glycosylation has been reported for many cellular processes and human diseases. The accumulated evidence points to the significant role these post-translational modifications play in aggregation and fibril formation. Simplified peptide model systems provide a means for investigating the molecular changes associated with protein aggregation. In this study, by using an amyloid-forming model peptide, we show that phosphorylation and glycosylation can affect folding and aggregation kinetics differently. Incorporation of phosphoserines, regardless of their quantity and position, turned out to be most efficient in preventing amyloid formation, whereas O-glycosylation has a more subtle effect. The introduction of a single beta-galactose does not change the folding behavior of the model peptide, but does alter the aggregation kinetics in a site-specific manner. The presence of multiple galactose residues has an effect similar to that of phosphorylation.

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Section: Peptidementioning

confidence: 99%

How Post‐Translational Modifications Influence Amyloid Formation: A Systematic Study of Phosphorylation and Glycosylation in Model Peptides

Broncel

Falenski

Wagner

et al. 2010

Chemistry A European J

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“…Additionally, amyloid formation in general is known to be a highly concentrationdependent process. [6] Thus, it can be assumed that the saltmediated coiled-coil conformation above a certain concentration does not provide enough stability to sufficiently compete with the urge of the system to convert into amyloids.…”

Section: I)mentioning

confidence: 99%

“…[2,3] Although amyloidforming proteins do not usually possess sequence homologies, impressive structural similarities, such as an unbranched morphology, diagnostic dye binding, and a characteristic X-ray diffraction pattern, are found for their fibrillar assemblies. [4][5][6] The soluble forms of the involved proteins…”

Section: Introductionmentioning

confidence: 99%

Intramolecular Charge Interactions as a Tool to Control the Coiled‐Coil‐to‐Amyloid Transformation

Pagel

Wagner

Araghi

et al. 2008

Chemistry A European J

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Under the influence of a changed environment, amyloid-forming proteins partially unfold and assemble into insoluble beta-sheet rich fibrils. Molecular-level characterization of these assembly processes has been proven to be very challenging, and for this reason several simplified model systems have been developed over recent years. Herein, we present a series of three de novo designed model peptides that adopt different conformations and aggregate morphologies depending on concentration, pH value, and ionic strength. The design strictly follows the characteristic heptad repeat of the alpha-helical coiled-coil structural motif. In all peptides, three valine residues, known to prefer the beta-sheet conformation, have been incorporated at the solvent-exposed b, c, and f positions to make the system prone to amyloid formation. Additionally, pH-controllable intramolecular electrostatic repulsions between equally charged lysine (peptide A) or glutamate (peptide B) residues were introduced along one side of the helical cylinder. The conformational behavior was monitored by circular dichroism spectroscopic analysis and thioflavin T fluorescence, and the resulting aggregates were further characterized by transmission electron microscopy. Whereas uninterrupted alpha-helical aggregates are found at neutral pH, Coulomb repulsions between lysine residues in peptide A destabilize the helical conformation at acidic pH values and trigger an assembly into amyloid-like fibrils. Peptide B features a glutamate-based switch functionality and exhibits opposite pH-dependent folding behavior. In this case, alpha-helical aggregates are found under acidic conditions, whereas amyloids are formed at neutral pH. To further validate the pH switch concept, peptide C was designed by including serine residues, thus resulting in an equal distribution of charged residues. Surprisingly, amyloid formation is observed at all pH values investigated for peptide C. The results of further investigations into the effect of different salts, however, strongly support the crucial role of intramolecular charge repulsions in the model system presented herein.

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“…[1][2][3] Furthermore, amyloids show interesting material properties which make them ideal candidates for the production of nanostructures and molecular nanobiomaterials, where building blocks may be varied by protein engineering techniques. [4,5] A rapidly emerging field is the control of aggregation by external means such as pH value or illumination of caged compounds, which allows the investigation of the basic principles of amyloid aggregation and the development of new nanobiomaterials.…”

mentioning

confidence: 99%

“…[1,17,18] Information on the size of aggregates was obtained by dynamic light, X-ray, and neutron scattering or by Fourier transform IR (FTIR) spectroscopy. [1,19] Herein we used FTIR spectroscopy, H-D exchange and TEM to characterize the aggregation of ac-AzoTrpZip2. FTIR yields quantitative information on the secondary structure and aggregation through the absorption bands in the 1615 to 1630 cm À1 range.…”

mentioning

confidence: 99%