Premium
Position‐Dependent Electrostatic Protection against Protein Aggregation
Author(s) -
Buell Alexander K.,
Tartaglia Gian Gaetano,
Birkett Neil R.,
Waudby Christopher A.,
Vendruscolo Michele,
Salvatella Xavier,
Welland Mark E.,
Dobson Christopher M.,
Knowles Tuomas P. J.
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900144
Subject(s) - amyloid fibril , fibril , protein aggregation , biophysics , aggregate (composite) , chemistry , rational design , position (finance) , electrostatics , amyloid (mycology) , amyloid β , biological system , nanotechnology , materials science , biochemistry , biology , finance , medicine , inorganic chemistry , disease , pathology , economics
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.