The Aggregation Free Energy Landscapes of Polyglutamine Repeats.

ABSTRACT: Aggregates of proteins containing polyglutamine (polyQ) repeats are strongly associated with several neurodegenerative diseases. The length of the repeats correlates with the severity of the disease. Previous studies have shown that pure polyQ peptides aggregate by nucleated growth polymerization and that the size of the critical nucleus (n*) decreases from tetrameric to dimeric and monomeric as length increases from Q₁₈ to Q₂₆. Why the critical nucleus size changes with repeat-length has been unclear. Using the associative memory, water-mediated, structure and energy model, we construct the aggregation free energy landscapes for polyQ peptides of different repeat-lengths. These studies show that the monomer of the shorter repeat-length (Q₂₀) prefers an ext

SUBMITTER: Chen M 

PROVIDER: S-EPMC5803750 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature