Proteins with a high propensity to aggregate can be largely prevented from doing so with surprisingly small changes to their primary structure. By using a combination of rational design and quantitative measurements of aggregation rates, we show that adding a single charge in specific "gatekeeper" regions is sufficient to change the timescale for amyloid fibril growth from minutes to weeks, thereby dramatically reducing the efficiency of this process.

Position-dependent electrostatic protection against protein aggregation / Buell, A. K.; Tartaglia, G. G.; Birkett, N. R.; Waudby, C. A.; Vendruscolo, M.; Salvatella, X.; Welland, M. E.; Dobson, C. M.; Knowles, T. P. J.. - In: CHEMBIOCHEM. - ISSN 1439-4227. - 10:8(2009), pp. 1309-1312. [10.1002/cbic.200900144]

Position-dependent electrostatic protection against protein aggregation

Tartaglia G. G.;Vendruscolo M.;
2009

Abstract

Proteins with a high propensity to aggregate can be largely prevented from doing so with surprisingly small changes to their primary structure. By using a combination of rational design and quantitative measurements of aggregation rates, we show that adding a single charge in specific "gatekeeper" regions is sufficient to change the timescale for amyloid fibril growth from minutes to weeks, thereby dramatically reducing the efficiency of this process.
2009
Amyloid; Atomic force microscopy; Biosensors; Gatekeeper residues; Protein aggregation; Algorithms; Amino Acid Substitution; Amyloid; Hydrophobic and Hydrophilic Interactions; Microscopy, Atomic Force; Mutation; Phosphatidylinositol 3-Kinases; Protein Structure, Tertiary; Static Electricity; src Homology Domains
01 Pubblicazione su rivista::01a Articolo in rivista
Position-dependent electrostatic protection against protein aggregation / Buell, A. K.; Tartaglia, G. G.; Birkett, N. R.; Waudby, C. A.; Vendruscolo, M.; Salvatella, X.; Welland, M. E.; Dobson, C. M.; Knowles, T. P. J.. - In: CHEMBIOCHEM. - ISSN 1439-4227. - 10:8(2009), pp. 1309-1312. [10.1002/cbic.200900144]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1451819
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