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.
Nanoscience Centre, University of Cambridge, J. J. Thomson Avenue, CB3 0FF, Cambridge, UK.
Alexander K
AK
Buell
Gian Gaetano
GG
Tartaglia
Neil R
NR
Birkett
Christopher A
CA
Waudby
Michele
M
Vendruscolo
Xavier
X
Salvatella
Mark E
ME
Welland
Christopher M
CM
Dobson
Tuomas P J
TP
Knowles
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