Position-dependent electrostatic protection against protein aggregation

Chembiochem. 2009 May 25;10(8):1309-12. doi: 10.1002/cbic.200900144.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Substitution
  • Amyloid / chemistry*
  • Hydrophobic and Hydrophilic Interactions
  • Microscopy, Atomic Force
  • Mutation
  • Phosphatidylinositol 3-Kinases / chemistry
  • Protein Structure, Tertiary
  • Static Electricity
  • src Homology Domains

Substances

  • Amyloid
  • Phosphatidylinositol 3-Kinases