TY - JOUR
T1 - Protein stickiness, rather than number of functional protein-protein interactions, predicts expression noise and plasticity in yeast
AU - Brettner, Leandra M.
AU - Masel, Joanna
N1 - Funding Information:
Work was supported by the National Institutes of Health (GM072733) and by the Howard Hughes Medical Institute (52005889) via the Undergraduate Biology Research Program at the University of Arizona. J.M. is a Pew Scholar in the Biomedical Sciences. We thank Andrew Capaldi and Scott Rifkin for helpful discussions, I. Ispolatov for helpful suggestions on an earlier version of this manuscript, and Ben Wilson for help with programming and MySQL.
PY - 2012/9/27
Y1 - 2012/9/27
N2 - Background: A hub protein is one that interacts with many functional partners. The annotation of hub proteins, or more generally the protein-protein interaction " degree" of each gene, requires quality genome-wide data. Data obtained using yeast two-hybrid methods contain many false positive interactions between proteins that rarely encounter each other in living cells, and such data have fallen out of favor.Results: We find that protein " stickiness" , measured as network degree in ostensibly low quality yeast two-hybrid data, is a more predictive genomic metric than the number of functional protein-protein interactions, as assessed by supposedly higher quality high throughput affinity capture mass spectrometry data. In the yeast Saccharomyces cerevisiae, a protein's high stickiness, but not its high number of functional interactions, predicts low stochastic noise in gene expression, low plasticity of gene expression across different environments, and high probability of forming a homo-oligomer. Our results are robust to a multiple regression analysis correcting for other known predictors including protein abundance, presence of a TATA box and whether a gene is essential. Once the higher stickiness of homo-oligomers is controlled for, we find that homo-oligomers have noisier and more plastic gene expression than other proteins, consistent with a role for homo-oligomerization in mediating robustness.Conclusions: Our work validates use of the number of yeast two-hybrid interactions as a metric for protein stickiness. Sticky proteins exhibit low stochastic noise in gene expression, and low plasticity in expression across different environments.
AB - Background: A hub protein is one that interacts with many functional partners. The annotation of hub proteins, or more generally the protein-protein interaction " degree" of each gene, requires quality genome-wide data. Data obtained using yeast two-hybrid methods contain many false positive interactions between proteins that rarely encounter each other in living cells, and such data have fallen out of favor.Results: We find that protein " stickiness" , measured as network degree in ostensibly low quality yeast two-hybrid data, is a more predictive genomic metric than the number of functional protein-protein interactions, as assessed by supposedly higher quality high throughput affinity capture mass spectrometry data. In the yeast Saccharomyces cerevisiae, a protein's high stickiness, but not its high number of functional interactions, predicts low stochastic noise in gene expression, low plasticity of gene expression across different environments, and high probability of forming a homo-oligomer. Our results are robust to a multiple regression analysis correcting for other known predictors including protein abundance, presence of a TATA box and whether a gene is essential. Once the higher stickiness of homo-oligomers is controlled for, we find that homo-oligomers have noisier and more plastic gene expression than other proteins, consistent with a role for homo-oligomerization in mediating robustness.Conclusions: Our work validates use of the number of yeast two-hybrid interactions as a metric for protein stickiness. Sticky proteins exhibit low stochastic noise in gene expression, and low plasticity in expression across different environments.
KW - Cooperativity
KW - Correlomics
KW - Evolutionary constraint
KW - Phenotypic plasticity
KW - Protein-protein interaction networks
KW - Stochastic gene expression
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U2 - 10.1186/1752-0509-6-128
DO - 10.1186/1752-0509-6-128
M3 - Article
C2 - 23017156
AN - SCOPUS:84866714615
SN - 1752-0509
VL - 6
JO - BMC Systems Biology
JF - BMC Systems Biology
M1 - 128
ER -