期刊
BMC SYSTEMS BIOLOGY
卷 6, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1752-0509-6-128
关键词
Protein-protein interaction networks; Stochastic gene expression; Evolutionary constraint; Correlomics; Cooperativity; Phenotypic plasticity
资金
- National Institutes of Health [GM072733]
- Howard Hughes Medical Institute via the Undergraduate Biology Research Program at the University of Arizona [52005889]
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.
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