17,417 research outputs found
Role-similarity based functional prediction in networked systems: Application to the yeast proteome
We propose a general method to predict functions of vertices where: 1. The
wiring of the network is somehow related to the vertex functionality. 2. A
fraction of the vertices are functionally classified. The method is influenced
by role-similarity measures of social network analysis. The two versions of our
prediction scheme is tested on model networks were the functions of the
vertices are designed to match their network surroundings. We also apply these
methods to the proteome of the yeast Saccharomyces cerevisiae and find the
results compatible with more specialized methods
Evolvability of Chaperonin Substrate Proteins
Molecular chaperones ensure that their substrate proteins reach the functional native state, and prevent their aggregation. Recently, an additional function was proposed for molecular chaperones: they serve as buffers (_capacitors_) for evolution by permitting their substrate proteins to mutate and at the same time still allowing them to fold productively.

Using pairwise alignments of _E. coli_ genes with genes from other gamma-proteobacteria, we showed that the described buffering effect cannot be observed among substrate proteins of GroEL, an essential chaperone in _E. coli_. Instead, we find that GroEL substrate proteins evolve less than other soluble _E. coli_ proteins. We analyzed several specific structural and biophysical properties of proteins to assess their influence on protein evolution and to find out why specifically GroEL substrates do not show the expected higher divergence from their orthologs.

Our results culminate in four main findings: *1.* We find little evidence that GroEL in _E. coli_ acts as a capacitor for evolution _in vivo_. *2.* GroEL substrates evolved less than other _E. coli_ proteins. *3.* Predominantly structural features appear to be a strong determinant of evolutionary rate. *4.* Besides size, hydrophobicity is a criterion for exclusion for a protein as a chaperonin substrate
Mapping the tail fiber as the receptor binding protein responsible for differential host specificity of Pseudomonas aeruginosa bacteriophages PaP1 and JG004.
The first step in bacteriophage infection is recognition and binding to the host receptor, which is mediated by the phage receptor binding protein (RBP). Different RBPs can lead to differential host specificity. In many bacteriophages, such as Escherichia coli and Lactococcal phages, RBPs have been identified as the tail fiber or protruding baseplate proteins. However, the tail fiber-dependent host specificity in Pseudomonas aeruginosa phages has not been well studied. This study aimed to identify and investigate the binding specificity of the RBP of P. aeruginosa phages PaP1 and JG004. These two phages share high DNA sequence homology but exhibit different host specificities. A spontaneous mutant phage was isolated and exhibited broader host range compared with the parental phage JG004. Sequencing of its putative tail fiber and baseplate region indicated a single point mutation in ORF84 (a putative tail fiber gene), which resulted in the replacement of a positively charged lysine (K) by an uncharged asparagine (N). We further demonstrated that the replacement of the tail fiber gene (ORF69) of PaP1 with the corresponding gene from phage JG004 resulted in a recombinant phage that displayed altered host specificity. Our study revealed the tail fiber-dependent host specificity in P. aeruginosa phages and provided an effective tool for its alteration. These contributions may have potential value in phage therapy
Generation and physiological roles of linear ubiquitin chains
Ubiquitination now ranks with phosphorylation as one of the best-studied post-translational modifications of proteins with broad regulatory roles across all of biology. Ubiquitination usually involves the addition of ubiquitin chains to target protein molecules, and these may be of eight different types, seven of which involve the linkage of one of the seven internal lysine (K) residues in one ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth, the so-called linear ubiquitin chains, the linkage is between the amino-terminal amino group of methionine on a ubiquitin that is conjugated with a target protein and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological roles are well established for K48-linked chains, which are essential for signaling proteasomal degradation of proteins, and for K63-linked chains, which play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis. We focus here on linear ubiquitin chains, how they are assembled, and how three different avenues of research have indicated physiological roles for linear ubiquitination in innate and adaptive immunity and suppression of inflammation
The bromodomain-containing protein Ibd1 links multiple chromatin related protein complexes to highly expressed genes in Tetrahymena thermophila
Background: The chromatin remodelers of the SWI/SNF family are critical
transcriptional regulators. Recognition of lysine acetylation through a
bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes,
this function is attributed to SNF2/Brg1.
Results: Using affinity purification coupled to mass spectrometry (AP-MS) we
identified members of a SWI/SNF complex (SWI/SNFTt) in Tetrahymena thermophila.
SWI/SNFTt is composed of 11 proteins, Snf5Tt, Swi1Tt, Swi3Tt, Snf12Tt, Brg1Tt,
two proteins with potential chromatin interacting domains and four proteins
without orthologs to SWI/SNF proteins in yeast or mammals. SWI/SNFTt subunits
localize exclusively to the transcriptionally active macronucleus (MAC) during
growth and development, consistent with a role in transcription. While
Tetrahymena Brg1 does not contain a BRD, our AP-MS results identified a
BRD-containing SWI/SNFTt component, Ibd1 that associates with SWI/SNFTt during
growth but not development. AP-MS analysis of epitope-tagged Ibd1 revealed it
to be a subunit of several additional protein complexes, including putative
SWRTt, and SAGATt complexes as well as a putative H3K4-specific histone methyl
transferase complex. Recombinant Ibd1 recognizes acetyl-lysine marks on
histones correlated with active transcription. Consistent with our AP-MS and
histone array data suggesting a role in regulation of gene expression, ChIP-Seq
analysis of Ibd1 indicated that it primarily binds near promoters and within
gene bodies of highly expressed genes during growth.
Conclusions: Our results suggest that through recognizing specific histones
marks, Ibd1 targets active chromatin regions of highly expressed genes in
Tetrahymena where it subsequently might coordinate the recruitment of several
chromatin remodeling complexes to regulate the transcriptional landscape of
vegetatively growing Tetrahymena cells.Comment: Published on BMC Epigenetics & Chromati
Drug-therapy networks and the predictions of novel drug targets
Recently, a number of drug-therapy, disease, drug, and drug-target networks
have been introduced. Here we suggest novel methods for network-based
prediction of novel drug targets and for improvement of drug efficiency by
analysing the effects of drugs on the robustness of cellular networks.Comment: This is an extended version of the Journal of Biology paper
containing 2 Figures, 1 Table and 44 reference
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