Position-dependent electrostatic protection against protein aggregation.
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.
Buell
Alexander K
AK
Nanoscience Centre, University of Cambridge, J. J. Thomson Avenue, CB3 0FF, Cambridge, UK.
Tartaglia
Gian Gaetano
GG
Birkett
Neil R
NR
Waudby
Christopher A
CA
Vendruscolo
Michele
M
Salvatella
Xavier
X
Welland
Mark E
ME
Dobson
Christopher M
CM
Knowles
Tuomas P J
TP
D000465:Algorithms; D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D018909:src Homology Domains
D000682:Amyloid; D019869:Phosphatidylinositol 3-Kinases