Polyglutamine shows a urea-like affinity for unfolded cytosolic protein
Polyglutamine shows a urea-like affinity for unfolded cytosolic protein
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.
Animals, Cell Line, Cytosol/chemistry, Humans, Huntington Disease, Microscopy, Confocal, Peptides/pharmacology, Protein Denaturation/drug effects, Protein Unfolding/drug effects, Proteins/drug effects, Thermodynamics, Urea
381-384
England, Jeremy L.
2f67b12b-9d45-4530-8d48-00034a22e9f9
Kaganovich, Daniel
ebb13f4e-e925-4aef-88e7-ddc25ef52d8f
21 January 2011
England, Jeremy L.
2f67b12b-9d45-4530-8d48-00034a22e9f9
Kaganovich, Daniel
ebb13f4e-e925-4aef-88e7-ddc25ef52d8f
England, Jeremy L. and Kaganovich, Daniel
(2011)
Polyglutamine shows a urea-like affinity for unfolded cytosolic protein.
FEBS Letters, 585 (2), .
(doi:10.1016/j.febslet.2010.12.023).
Abstract
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.
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Accepted/In Press date: 19 December 2010
Published date: 21 January 2011
Additional Information:
Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Keywords:
Animals, Cell Line, Cytosol/chemistry, Humans, Huntington Disease, Microscopy, Confocal, Peptides/pharmacology, Protein Denaturation/drug effects, Protein Unfolding/drug effects, Proteins/drug effects, Thermodynamics, Urea
Identifiers
Local EPrints ID: 474250
URI: http://eprints.soton.ac.uk/id/eprint/474250
ISSN: 0014-5793
PURE UUID: 476035d0-15b6-478c-aaba-0dfdbadbde3f
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Date deposited: 16 Feb 2023 18:00
Last modified: 17 Mar 2024 04:17
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Contributors
Author:
Jeremy L. England
Author:
Daniel Kaganovich
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