@article {49757, title = {Evolutionarily conserved network properties of intrinsically disordered proteins.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0126729}, abstract = {

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.

}, keywords = {Animals, Cluster Analysis, Databases, Protein, Drosophila, Drosophila Proteins, Evolution, Molecular, HUMANS, Intrinsically Disordered Proteins, Metabolic Networks and Pathways, Mice, Osmotic Pressure, Protein Interaction Maps, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins}, issn = {1932-6203}, doi = {10.1371/journal.pone.0126729}, author = {Rangarajan, Nivedita and Kulkarni, Prakash and Hannenhalli, Sridhar} } @article {49548, title = {Quantitative measurement of allele-specific protein expression in a diploid yeast hybrid by LC-MS.}, volume = {8}, year = {2012}, month = {2012}, pages = {602}, abstract = {

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.

}, keywords = {Alleles, Chromatography, Liquid, Fungal Proteins, Gene Expression Profiling, Gene Expression Regulation, Fungal, HUMANS, Mass Spectrometry, proteomics, Regression Analysis, Saccharomyces, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Species Specificity}, issn = {1744-4292}, doi = {10.1038/msb.2012.34}, author = {Khan, Zia and Bloom, Joshua S and Amini, Sasan and Singh, Mona and Perlman, David H and Caudy, Amy A and Kruglyak, Leonid} } @article {49749, title = {Measuring differential gene expression by short read sequencing: quantitative comparison to 2-channel gene expression microarrays.}, journal = {BMC Genomics}, volume = {10}, year = {2009}, month = {2009}, pages = {221}, abstract = {

BACKGROUND: High-throughput cDNA synthesis and sequencing of poly(A)-enriched RNA is rapidly emerging as a technology competing to replace microarrays as a quantitative platform for measuring gene expression.

RESULTS: Consequently, we compared full length cDNA sequencing to 2-channel gene expression microarrays in the context of measuring differential gene expression. Because of its comparable cost to a gene expression microarray, our study focused on the data obtainable from a single lane of an Illumina 1 G sequencer. We compared sequencing data to a highly replicated microarray experiment profiling two divergent strains of S. cerevisiae.

CONCLUSION: Using a large number of quantitative PCR (qPCR) assays, more than previous studies, we found that neither technology is decisively better at measuring differential gene expression. Further, we report sequencing results from a diploid hybrid of two strains of S. cerevisiae that indicate full length cDNA sequencing can discover heterozygosity and measure quantitative allele-specific expression simultaneously.

}, keywords = {algorithms, DNA, Complementary, DNA, Fungal, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Saccharomyces cerevisiae, sequence alignment, Sequence Analysis, DNA}, issn = {1471-2164}, doi = {10.1186/1471-2164-10-221}, author = {Bloom, Joshua S and Khan, Zia and Kruglyak, Leonid and Singh, Mona and Caudy, Amy A} } @article {38368, title = {MDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases}, journal = {BiochemistryBiochemistry}, volume = {40}, year = {2001}, note = {http://www.ncbi.nlm.nih.gov/pubmed/11601995?dopt=Abstract}, abstract = {MDP-1 is a eukaryotic magnesium-dependent acid phosphatase with little sequence homology to previously characterized phosphatases. The presence of a conserved motif (Asp-X-Asp-X-Thr) in the N terminus of MDP-1 suggested a relationship to the haloacid dehalogenase (HAD) superfamily, which contains a number of magnesium-dependent acid phosphatases. These phosphatases utilize an aspartate nucleophile and contain a number of conserved active-site residues and hydrophobic patches, which can be plausibly aligned with conserved residues in MDP-1. Seven site-specific point mutants of MDP-1 were produced by modifying the catalytic aspartate, serine, and lysine residues to asparagine or glutamate, alanine, and arginine, respectively. The activity of these mutants confirms the assignment of MDP-1 as a member of the HAD superfamily. Detailed comparison of the sequence of the 15 MDP-1 sequences from various organisms with other HAD superfamily sequences suggests that MDP-1 is not closely related to any particular member of the superfamily. The crystal structures of several HAD family enzymes identify a domain proximal to the active site responsible for important interactions with low molecular weight substrates. The absence of this domain or any other that might perform the same function in MDP-1 suggests an "open" active site capable of interactions with large substrates such as proteins. This suggestion was experimentally confirmed by demonstration that MDP-1 is competent to catalyze the dephosphorylation of tyrosine-phosphorylated proteins.}, keywords = {Amino Acid Motifs, Amino Acid Sequence, Animals, Aspartic Acid, Catalytic Domain, HUMANS, Hydrolases, Mice, Molecular Sequence Data, Multigene Family, Mutagenesis, Site-Directed, Phosphoprotein Phosphatases, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Rats, Saccharomyces cerevisiae, sequence alignment, Sequence Homology, Amino Acid}, author = {J. Selengut} } @article {49712, title = {RNA processing. Sequences that signal where to splice.}, journal = {Nature}, volume = {304}, year = {1983}, pages = {309-10}, keywords = {Base Sequence, RNA Splicing, Saccharomyces cerevisiae}, issn = {0028-0836}, author = {Mount, S M} }