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Polyglutamine shows a urea‐like affinity for unfolded cytosolic protein
Author(s) -
England Jeremy L.,
Kaganovich Daniel
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.12.023
Subject(s) - proteostasis , cytosol , biophysics , glutamine , urea , chemistry , neurodegeneration , biochemistry , protein folding , amino acid , protein aggregation , unfolded protein response , microbiology and biotechnology , biology , endoplasmic reticulum , enzyme , medicine , disease , pathology
Noting that the glutamine (Q) amino acid side‐chain bears a striking resemblance to urea, the chemical denaturant, we argue on biophysical grounds that polyQ chains should possess a potent denaturant activity. Using live‐cell confocal microscopy, we demonstrate that the surface of a polyQ inclusion denatures cytosolic proteins by binding and trapping them in an immobilized ring. We also show the reverse effect: that elevated local concentrations of unfolded protein in the cytosol can drive the co‐localization and accumulation of short polyQ tracts that normally do not aggregate. Such a urea‐like mechanism explains many past observations about polyQ‐driven disruption of proteostasis and neurodegeneration.