Sudip Kundu

Bio: Sudip Kundu is an academic researcher from University of Calcutta. The author has contributed to research in topics: Protein folding & Ribosomal protein. The author has an hindex of 14, co-authored 60 publications receiving 810 citations.

RNA-protein coevolution study of Gemin5 uncovers the role of the PXSS motif of RBS1 domain for RNA binding

Abstract: Regulation of protein synthesis is an essential step of gene expression. This process is under the control of cis-acting RNA elements and trans-acting factors. Gemin5 is a multifunctional RNA-binding protein organized in distinct domains. The protein bears a non-canonical RNA-binding site, designated RBS1, at the C-terminal end. Among other cellular RNAs, the RBS1 region recognizes a sequence located within the coding region of Gemin5 mRNA, termed H12. Expression of RBS1 stimulates translation of RNA reporters carrying the H12 sequence, counteracting the negative effect of Gemin5 on global protein synthesis. A computational analysis of RBS1 protein and H12 RNA variability across the evolutionary scale predicts coevolving pairs of amino acids and nucleotides. RBS1 footprint and gel-shift assays indicated a positive correlation between the identified coevolving pairs and RNA-protein interaction. The coevolving residues of RBS1 contribute to the recognition of stem-loop SL1, an RNA structural element of H12 that contains the coevolving nucleotides. Indeed, RBS1 proteins carrying substitutions on the coevolving residues P1297 or S1299S1300, drastically reduced SL1-binding. Unlike the wild type RBS1 protein, expression of these mutant proteins in cells failed to enhance translation stimulation of mRNA reporters carrying the H12 sequence. Therefore, the PXSS motif within the RBS1 domain of Gemin5 and the RNA structural motif SL1 of its mRNA appears to play a key role in fine-tuning the expression level of this essential protein.

Modular Organization of Residue-Level Contacts Shapes the Selection Pressure on Individual Amino Acid Sites of Ribosomal Proteins.

Abstract: Understanding the molecular evolution of macromolecular complexes in the light of their structure, assembly, and stability is of central importance. Here, we address how the modular organization of native molecular contacts shapes the selection pressure on individual residue sites of ribosomal complexes. The bacterial ribosomal complex is represented as a residue contact network where nodes represent amino acid/nucleotide residues and edges represent their van der Waals interactions. We find statistically overrepresented native amino acid-nucleotide contacts (OaantC, one amino acid contacts one or multiple nucleotides, internucleotide contacts are disregarded). Contact number is defined as the number of nucleotides contacted. Involvement of individual amino acids in OaantCs with smaller contact numbers is more random, whereas only a few amino acids significantly contribute to OaantCs with higher contact numbers. An investigation of structure, stability, and assembly of bacterial ribosome depicts the involvement of these OaantCs in diverse biophysical interactions stabilizing the complex, including high-affinity protein-RNA contacts, interprotein cooperativity, intersubunit bridge, packing of multiple ribosomal RNA domains, etc. Amino acid-nucleotide constituents of OaantCs with higher contact numbers are generally associated with significantly slower substitution rates compared with that of OaantCs with smaller contact numbers. This evolutionary rate heterogeneity emerges from the strong purifying selection pressure that conserves the respective amino acid physicochemical properties relevant to the stabilizing interaction with OaantC nucleotides. An analysis of relative molecular orientations of OaantC residues and their interaction energetics provides the biophysical ground of purifying selection conserving OaantC amino acid physicochemical properties.

Do topological parameters of amino acids within protein contact networks depend on their physico-chemical properties?

Abstract: The three dimensional structure of a protein is determined by the interactions of its constituent amino acids. Considering the amino acids as nodes and the non-bonded interactions among them in 3D space as edges, researchers have constructed protein contact networks and analyzed the values of several topological parameters to uncover different important aspects of proteins. Here, we have analyzed some of the topological parameters such as degree, strength, clustering coefficients, betweenness and closeness centrality of each of the twenty amino acids in a set of non-redundant proteins covering all classes and folds. The results show that the values of these topological parameters vary widely with different amino acids. Also, these values differ significantly with different length scales of proteins. Most of the hydrophobic residues along with Cys, Arg and His have larger contributions to the long range connectivities than short range. We have also studied whether the values of topological parameters have any significant dependency on the physico-chemical properties of the amino acids. While the clustering coefficients show a strong negative correlation with residual volumes, surface areas and number of atoms in the side chains of amino acids; the degrees, strengths and betweenness show positive correlations with the mentioned properties. All the topological parameters show high dependency on bulkiness and average area buried of the amino acid residues in all-range residue networks. The average degree shows higher dependency on hydrophobicity, while the average strength is more able to capture the essences of surface area, residual volume and number of atoms of amino acids. The hydrophobicities of the amino acids and their corresponding degrees show a higher positive correlation in long range networks (LRNs) than short range networks (SRNs). The closeness centrality shows high correlation with two hydrophobic scales and no correlation with surface area, residual volume or number of atoms in LRNs. We have further explored the relationship in hydrophobic, hydrophilic and charged residues separately. Interestingly, charged residues show a higher dependency on the number of atoms than their residual volumes and surface areas. Finally, we present a linear regression model relating the network parameters with physico-chemical properties of amino acids.

Random graphs

Abstract: We will review some of the major results in random graphs and some of the more challenging open problems. We will cover algorithmic and structural questions. We will touch on newer models, including those related to the WWW.

Hierarchical Organization of Human Cortical Networks in Health and Schizophrenia

Abstract: The complex organization of connectivity in the human brain is incompletely understood. Recently, topological measures based on graph theory have provided a new approach to quantify large-scale cortical networks. These methods have been applied to anatomical connectivity data on nonhuman species, and cortical networks have been shown to have small-world topology, associated with high local and global efficiency of information transfer. Anatomical networks derived from cortical thickness measurements have shown the same organizational properties of the healthy human brain, consistent with similar results reported in functional networks derived from resting state functional magnetic resonance imaging (MRI) and magnetoencephalographic data. Here we show, using anatomical networks derived from analysis of inter-regional covariation of gray matter volume in MRI data on 259 healthy volunteers, that classical divisions of cortex (multimodal, unimodal, and transmodal) have some distinct topological attributes. Although all cortical divisions shared nonrandom properties of small-worldness and efficient wiring (short mean Euclidean distance between connected regions), the multimodal network had a hierarchical organization, dominated by frontal hubs with low clustering, whereas the transmodal network was assortative. Moreover, in a sample of 203 people with schizophrenia, multimodal network organization was abnormal, as indicated by reduced hierarchy, the loss of frontal and the emergence of nonfrontal hubs, and increased connection distance. We propose that the topological differences between divisions of normal cortex may represent the outcome of different growth processes for multimodal and transmodal networks and that neurodevelopmental abnormalities in schizophrenia specifically impact multimodal cortical organization.

MicroRNAs: Target Recognition and Regulatory Functions

Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.