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Title: An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins
Authors: De Baets, Greet
Reumers, Joke
Delgado Blanco, Javier
Dopazo, Joaquin
Schymkowitz, Joost
Rousseau, Frederic # ×
Issue Date: Jun-2011
Publisher: Public Library of Science
Series Title: PLoS Computational Biology vol:7 issue:6
Article number: e1002090
Abstract: We previously showed the existence of selective pressure against protein aggregation by the enrichment of aggregation-opposing 'gatekeeper' residues at strategic places along the sequence of proteins. Here we analyzed the relationship between protein lifetime and protein aggregation by combining experimentally determined turnover rates, expression data, structural data and chaperone interaction data on a set of more than 500 proteins. We find that selective pressure on protein sequences against aggregation is not homogeneous but that short-living proteins on average have a higher aggregation propensity and fewer chaperone interactions than long-living proteins. We also find that short-living proteins are more often associated to deposition diseases. These findings suggest that the efficient degradation of high-turnover proteins is sufficient to preclude aggregation, but also that factors that inhibit proteasomal activity, such as physiological ageing, will primarily affect the aggregation of short-living proteins.
URI: 
ISSN: 1553-734X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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