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Open Access Research article

Protein stickiness, rather than number of functional protein-protein interactions, predicts expression noise and plasticity in yeast

Leandra M Brettner12 and Joanna Masel1*

Author affiliations

1 Present address: Ecology & Evolutionary Biology, University of Arizona, 1041 E Lowell St, Tucson, AZ, 85721, USA

2 Present address: Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98195, USA

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Citation and License

BMC Systems Biology 2012, 6:128  doi:10.1186/1752-0509-6-128

Published: 27 September 2012

Abstract

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.

Keywords:
Protein-protein interaction networks; Stochastic gene expression; Evolutionary constraint; Correlomics; Cooperativity; Phenotypic plasticity