Reference: Chen Y and Dokholyan NV (2008) Natural selection against protein aggregation on self-interacting and essential proteins in yeast, fly, and worm. Mol Biol Evol 25(8):1530-3

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Abstract


Protein aggregation is the phenomenon of protein self-association potentially leading to detrimental effects on physiology, which is closely related to numerous human diseases such as Alzheimer's and Parkinson's disease. Despite progress in understanding the mechanism of protein aggregation, how natural selection against protein aggregation acts on subunits of protein complexes and on proteins with different contributions to organism fitness remains largely unknown. Here, we perform a proteome-wide analysis by using an experimentally validated algorithm TANGO and utilizing sequence, interactomic and phenotype-based functional genomic data from yeast, fly, and nematode. We find that proteins that are capable of forming homooligomeric complex have lower aggregation propensity compared with proteins that do not function as homooligomer. Further, proteins that are essential to the fitness of an organism have lower aggregation propensity compared with nonessential ones. Our finding suggests that the selection force against protein aggregation acts across different hierarchies of biological system.

Reference Type
Comparative Study | Letter | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Chen Y, Dokholyan NV
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