TY - JOUR T1 - Evolutionarily conserved network properties of intrinsically disordered proteins. JF - PLoS One Y1 - 2015 A1 - Rangarajan, Nivedita A1 - Kulkarni, Prakash A1 - Hannenhalli, Sridhar KW - Animals KW - Cluster Analysis KW - Databases, Protein KW - Drosophila KW - Drosophila Proteins KW - Evolution, Molecular KW - HUMANS KW - Intrinsically Disordered Proteins KW - Metabolic Networks and Pathways KW - Mice KW - Osmotic Pressure KW - Protein Interaction Maps KW - Saccharomyces cerevisiae KW - Saccharomyces cerevisiae Proteins AB -

BACKGROUND: Intrinsically disordered proteins (IDPs) lack a stable tertiary structure in isolation. Remarkably, however, a substantial portion of IDPs undergo disorder-to-order transitions upon binding to their cognate partners. Structural flexibility and binding plasticity enable IDPs to interact with a broad range of partners. However, the broader network properties that could provide additional insights into the functional role of IDPs are not known.

RESULTS: Here, we report the first comprehensive survey of network properties of IDP-induced sub-networks in multiple species from yeast to human. Our results show that IDPs exhibit greater-than-expected modularity and are connected to the rest of the protein interaction network (PIN) via proteins that exhibit the highest betweenness centrality and connect to fewer-than-expected IDP communities, suggesting that they form critical communication links from IDP modules to the rest of the PIN. Moreover, we found that IDPs are enriched at the top level of regulatory hierarchy.

CONCLUSION: Overall, our analyses reveal coherent and remarkably conserved IDP-centric network properties, namely, modularity in IDP-induced network and a layer of critical nodes connecting IDPs with the rest of the PIN.

VL - 10 CP - 5 M3 - 10.1371/journal.pone.0126729 ER - TY - Generic T1 - Quantitative measurement of allele-specific protein expression in a diploid yeast hybrid by LC-MS. Y1 - 2012 A1 - Khan, Zia A1 - Bloom, Joshua S A1 - Amini, Sasan A1 - Singh, Mona A1 - Perlman, David H A1 - Caudy, Amy A A1 - Kruglyak, Leonid KW - Alleles KW - Chromatography, Liquid KW - Fungal Proteins KW - Gene Expression Profiling KW - Gene Expression Regulation, Fungal KW - HUMANS KW - Mass Spectrometry KW - proteomics KW - Regression Analysis KW - Saccharomyces KW - Saccharomyces cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Species Specificity AB -

Understanding the genetic basis of gene regulatory variation is a key goal of evolutionary and medical genetics. Regulatory variation can act in an allele-specific manner (cis-acting) or it can affect both alleles of a gene (trans-acting). Differential allele-specific expression (ASE), in which the expression of one allele differs from another in a diploid, implies the presence of cis-acting regulatory variation. While microarrays and high-throughput sequencing have enabled genome-wide measurements of transcriptional ASE, methods for measurement of protein ASE (pASE) have lagged far behind. We describe a flexible, accurate, and scalable strategy for measurement of pASE by liquid chromatography-coupled mass spectrometry (LC-MS). We apply this approach to a hybrid between the yeast species Saccharomyces cerevisiae and Saccharomyces bayanus. Our results provide the first analysis of the relative contribution of cis-acting and trans-acting regulatory differences to protein expression divergence between yeast species.

JA - Mol Syst Biol VL - 8 M3 - 10.1038/msb.2012.34 ER -