Bioinformatic exploration reveals features of tenpIN family of type III toxin-antitoxin systems in bacteria and viruses.

Toxin-antitoxin (TA) systems in bacteria consist of two genes: one encoding a toxin that inhibits essential cellular processes and the other encoding an antitoxin that neutralizes the toxin under homeostatic conditions. TA systems are classified into eight types (I to VIII) based on the mechanism of toxin inhibition by the antitoxin. Type III TA systems comprise a protein toxin that is usually an endoribonuclease and an RNA antitoxin and are further classified into toxIN, cptIN, and tenpIN families based on toxin sequence homology.

The alteration of structural network upon transient association between proteins studied using graph theory.

Proteins such as enzymes perform their function by predominant non-covalent bond interactions between transiently interacting units. There is an impact on the overall structural topology of the protein, albeit transient nature of such interactions, that enable proteins to deactivate or activate. This aspect of the alteration of the structural topology is studied by employing protein structural networks, which are node-edge representative models of protein structure, reported as a robust tool for capturing interactions between residues.

Computational tools to study RNA-protein complexes.

RNA is the key player in many cellular processes such as signal transduction, replication, transport, cell division, transcription, and translation. These diverse functions are accomplished through interactions of RNA with proteins. However, protein-RNA interactions are still poorly derstood in contrast to protein-protein and protein-DNA interactions.

Profiles of Natural and Designed Protein-Like Sequences Effectively Bridge Protein Sequence Gaps: Implications in Distant Homology Detection.

Sequence-based approaches are fundamental to guide experimental investigations in obtaining structural and/or functional insights into uncharacterized protein families. Powerful profile-based sequence search methods rely on a sequence space continuum to identify non-trivial relationships through homology detection. The computational design of protein-like sequences that serve as "artificial linkers" is useful in identifying relationships between distant members of a structural fold.

Sequence Divergence and Functional Specializations of the Ancient Spliceosomal SF3b: Implications in Flexibility and Adaptations of the Multi-Protein Complex.

Multi-protein assemblies are complex molecular systems that perform highly sophisticated biochemical functions in an orchestrated manner. They are subject to changes that are governed by the evolution of individual components. We performed a comparative analysis of the ancient and functionally conserved spliceosomal SF3b complex, to recognize molecular signatures that contribute to sequence divergence and functional specializations.

Rewards of divergence in sequences, 3-D structures and dynamics of yeast and human spliceosome SF3b complexes.

The evolution of homologous and functionally equivalent multiprotein assemblies is intriguing considering sequence divergence of constituent proteins. Here, we studied the implications of protein sequence divergence on the structure, dynamics and function of homologous yeast and human SF3b spliceosomal subcomplexes. Human and yeast SF3b comprise of 7 and 6 proteins respectively, with all yeast proteins homologous to their human counterparts at moderate sequence identity.

Identification, functional characterization, assembly and structure of ToxIN type III toxin-antitoxin complex from E. coli.

Toxin-antitoxin (TA) systems are proposed to play crucial roles in bacterial growth under stress conditions such as phage infection. The type III TA systems consist of a protein toxin whose activity is inhibited by a noncoding RNA antitoxin. The toxin is an endoribonuclease, while the antitoxin consists of multiple repeats of RNA.

Comparative Analysis of Structural and Dynamical Features of Ribosome Upon Association With mRNA Reveals Potential Role of Ribosomal Proteins.

Ribosomes play a critical role in maintaining cellular proteostasis. The binding of messenger RNA (mRNA) to the ribosome regulates kinetics of protein synthesis. To generate an understanding of the structural, mechanistic, and dynamical features of mRNA recognition in the ribosome, we have analysed mRNA-protein interactions through a structural comparison of the ribosomal complex in the presence and absence of mRNA.

Signatures of conserved and unique molecular features in Afrotheria.

Afrotheria is a clade of African-origin species with striking dissimilarities in appearance and habitat. In this study, we compared whole proteome sequences of six Afrotherian species to obtain a broad viewpoint of their underlying molecular make-up, to recognize potentially unique proteomic signatures. We find that 62% of the proteomes studied here, predominantly involved in metabolism, are orthologous, while the number of homologous proteins between individual species is as high as 99.

Molecular and Structural Basis of Cross-Reactivity in Toxin-Antitoxin Systems.

genome encodes over 80 toxin-antitoxin (TA) systems. While each toxin interacts with its cognate antitoxin, the abundance of TA systems presents an opportunity for potential non-cognate interactions. TA systems mediate manifold interactions to manage pathogenicity and stress response network of the cell and non-cognate interactions may play vital roles as well.

Artificial protein sequences enable recognition of vicinal and distant protein functional relationships.

High divergence in protein sequences makes the detection of distant protein relationships through homology-based approaches challenging. Grouping protein sequences into families, through similarities in either sequence or 3-D structure, facilitates in the improved recognition of protein relationships. In addition, strategically designed protein-like sequences have been shown to bridge distant structural domain families by serving as artificial linkers.

Bioinformatic and mutational studies of related toxin-antitoxin pairs in predict and identify key functional residues.

possesses an unusually large representation of type II toxin-antitoxin (TA) systems, whose functions and targets are mostly unknown. To better understand the basis of their unique expansion and to probe putative functional similarities among these systems, here we computationally and experimentally investigated their sequence relationships. Bioinformatic and phylogenetic investigations revealed that 51 sequences of the VapBC toxin family group into paralogous sub-clusters.

Mycobacterium tuberculosis Rv0366c-Rv0367c encodes a non-canonical PezAT-like toxin-antitoxin pair.

Toxin-antitoxin (TA) systems are ubiquitously existing addiction modules with essential roles in bacterial persistence and virulence. The genome of Mycobacterium tuberculosis encodes approximately 79 TA systems. Through computational and experimental investigations, we report for the first time that Rv0366c-Rv0367c is a non-canonical PezAT-like toxin-antitoxin system in M.

Domain architecture of BAF250a reveals the ARID and ARM-repeat domains with implication in function and assembly of the BAF remodeling complex.

BAF250a and BAF250b are subunits of the SWI/SNF chromatin-remodeling complex that recruit the complex to chromatin allowing transcriptional activation of several genes. Despite being the central subunits of the SWI/SNF complex, the structural and functional annotation of BAF250a/b remains poorly understood. BAF250a (nearly 2200 residues protein) harbors an N-terminal DNA binding ARID (~110 residues) and a C-terminal folded region (~250 residues) of unknown structure and function, recently annotated as BAF250_C.

Use of designed sequences in protein structure recognition.

Background: Knowledge of the protein structure is a pre-requisite for improved understanding of molecular function. The gap in the sequence-structure space has increased in the post-genomic era. Grouping related protein sequences into families can aid in narrowing the gap.

Probing the Most Stable Isomer of Zirconium Bis(phenoxy-imine) Cation: A Computational Investigation.

The possibility of coexistence of multiple isomers for zirconium bis(phenoxy-imine) catalyst has been systematically studied by computational approaches. The energetics among the five different isomers of neutral Zr-catalyst have been assessed quantum mechanically. The results suggest that isomer cis-N/trans-O/cis-Me is the most stable among the five isomers in accordance with the general observations of these kinds of phenoxy-imine catalyst.

Protein sequence design and its applications.

Design of proteins has far-reaching potentials in diverse areas that span repurposing of the protein scaffold for reactions and substrates that they were not naturally meant for, to catching a glimpse of the ephemeral proteins that nature might have sampled during evolution. These non-natural proteins, either in synthesized or virtual form have opened the scope for the design of entities that not only rival their natural counterparts but also offer a chance to visualize the protein space continuum that might help to relate proteins and understand their associations. Here, we review the recent advances in protein engineering and design, in multiple areas, with a view to drawing attention to their future potential.

De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods.

Background: In the post-genomic era where sequences are being determined at a rapid rate, we are highly reliant on computational methods for their tentative biochemical characterization. The Pfam database currently contains 3,786 families corresponding to "Domains of Unknown Function" (DUF) or "Uncharacterized Protein Family" (UPF), of which 3,087 families have no reported three-dimensional structure, constituting almost one-fourth of the known protein families in search for both structure and function.

Results: We applied a 'computational structural genomics' approach using five state-of-the-art remote similarity detection methods to detect the relationship between uncharacterized DUFs and domain families of known structures.

CHEXVIS: a tool for molecular channel extraction and visualization.

Background: Understanding channel structures that lead to active sites or traverse the molecule is important in the study of molecular functions such as ion, ligand, and small molecule transport. Efficient methods for extracting, storing, and analyzing protein channels are required to support such studies. Further, there is a need for an integrated framework that supports computation of the channels, interactive exploration of their structure, and detailed visual analysis of their properties.

NrichD database: sequence databases enriched with computationally designed protein-like sequences aid in remote homology detection.

NrichD (http://proline.biochem.iisc.

Mapping post-translational modifications of mammalian testicular specific histone variant TH2B in tetraploid and haploid germ cells and their implications on the dynamics of nucleosome structure.

Histones regulate a variety of chromatin templated events by their post-translational modifications (PTMs). Although there are extensive reports on the PTMs of canonical histones, the information on the histone variants remains very scanty. Here, we report the identification of different PTMs, such as acetylation, methylation, and phosphorylation of a major mammalian histone variant TH2B.

Structural Annotation of the Mycobacterium tuberculosis Proteome.

Efforts from the TB Structural Genomics Consortium together with those of tuberculosis structural biologists worldwide have led to the determination of about 350 structures, making up nearly a tenth of the pathogen's proteome. Given that knowledge of protein structures is essential to obtaining a high-resolution understanding of the underlying biology, it is desirable to have a structural view of the entire proteome. Indeed, structure prediction methods have advanced sufficiently to allow structural models of many more proteins to be built based on homology modeling and fold recognition strategies.

Filling-in void and sparse regions in protein sequence space by protein-like artificial sequences enables remarkable enhancement in remote homology detection capability.

Protein functional annotation relies on the identification of accurate relationships, sequence divergence being a key factor. This is especially evident when distant protein relationships are demonstrated only with three-dimensional structures. To address this challenge, we describe a computational approach to purposefully bridge gaps between related protein families through directed design of protein-like "linker" sequences.

Improved detection of remote homologues using cascade PSI-BLAST: influence of neighbouring protein families on sequence coverage.

Background: Development of sensitive sequence search procedures for the detection of distant relationships between proteins at superfamily/fold level is still a big challenge. The intermediate sequence search approach is the most frequently employed manner of identifying remote homologues effectively. In this study, examination of serine proteases of prolyl oligopeptidase, rhomboid and subtilisin protein families were carried out using plant serine proteases as queries from two genomes including A.

Structural annotation of Mycobacterium tuberculosis proteome.

Of the ∼4000 ORFs identified through the genome sequence of Mycobacterium tuberculosis (TB) H37Rv, experimentally determined structures are available for 312. Since knowledge of protein structures is essential to obtain a high-resolution understanding of the underlying biology, we seek to obtain a structural annotation for the genome, using computational methods. Structural models were obtained and validated for ∼2877 ORFs, covering ∼70% of the genome.