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Structure based approach for understanding organism specific recognition of protein-RNA complexes.

Nagarajan R, Chothani SP, Ramakrishnan C, Sekijima M, Gromiha MM - Biol. Direct (2015)

Bottom Line: We found that the proteins of mesophilic organisms have more number of binding sites than thermophiles and the binding propensities of amino acid residues are distinct in E. coli, H. sapiens, S. cerevisiae, thermophiles and archaea.Based on structural analysis and molecular dynamics simulations we suggest that the mode of recognition depends on the type of the organism in a protein-RNA complex.This article was reviewed by Sandor Pongor, Gajendra Raghava and Narayanaswamy Srinivasan.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Bhupat Jyoti Metha School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, Tamilnadu, India. nagabioinfostar@gmail.com.

ABSTRACT

Background: Protein-RNA interactions perform diverse functions within the cell. Understanding the recognition mechanism of protein-RNA complexes has been a challenging task in molecular and computational biology. In earlier works, the recognition mechanisms have been studied for a specific complex or using a set of non-redundant complexes. In this work, we have constructed 18 sets of same protein-RNA complexes belonging to different organisms from Protein Data Bank (PDB). The similarities and differences in each set of complexes have been revealed in terms of various sequence and structure based features such as root mean square deviation, sequence homology, propensity of binding site residues, variance, conservation at binding sites, binding segments, binding motifs of amino acid residues and nucleotides, preferred amino acid-nucleotide pairs and influence of neighboring residues for binding.

Results: We found that the proteins of mesophilic organisms have more number of binding sites than thermophiles and the binding propensities of amino acid residues are distinct in E. coli, H. sapiens, S. cerevisiae, thermophiles and archaea. Proteins prefer to bind with RNA using a single residue segment in all the organisms while RNA prefers to use a stretch of up to six nucleotides for binding with proteins. We have developed amino acid residue-nucleotide pair potentials for different organisms, which could be used for predicting the binding specificity. Further, molecular dynamics simulation studies on aspartyl tRNA synthetase complexed with aspartyl tRNA showed specific modes of recognition in E. coli, T. thermophilus and S. cerevisiae.

Conclusion: Based on structural analysis and molecular dynamics simulations we suggest that the mode of recognition depends on the type of the organism in a protein-RNA complex.

Reviewers: This article was reviewed by Sandor Pongor, Gajendra Raghava and Narayanaswamy Srinivasan.

No MeSH data available.


Related in: MedlinePlus

Structure based sequence alignment of aspartyl tRNA complexes, 1ASY, 1EFW and 1IL2. The structurally conserved regions are shown in boxes. The interacting residues are highlighted with bold letters.
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Fig4: Structure based sequence alignment of aspartyl tRNA complexes, 1ASY, 1EFW and 1IL2. The structurally conserved regions are shown in boxes. The interacting residues are highlighted with bold letters.

Mentions: We have extensively studied the variation of binding site residues in different organisms for each protein-RNA complex and the normalized binding propensities of 20 amino acid residues for a typical complex, AspRS-tRNAAsp from E. coli, T. thermophilus and S. cerevisiae are shown in Table 5. We observed that the binding mode and binding site residues are distinct in these organisms. Phe prefers to be in the binding sites in E. coli whereas Gly is prefered in T. thermophilus and Pro, Met and Thr are prefered in S. cerevisiae. Although Asn, Glu and Arg show preference to be at the interface in all the organisms, the strength is different among them. The preference of Arg was higher in E. coli and T. thermophilus than Lys whereas an opposite trend was observed in S. cerevisiae. The structure based sequence alignment of AspRS from three different organisms is shown in Figure 4. We observed that the binding site residues, binding mode and binding segments are different among the three different organisms in the considered complex. The analysis of binding segments showed a similar trend at the protein level however the behavior is different in RNA among different organisms. Single nucleotide segments accommodated 67% of the binding sites in T. thermophilus whereas only 33% of the binding sites have single nucleotide segments in E. coli.Table 5


Structure based approach for understanding organism specific recognition of protein-RNA complexes.

Nagarajan R, Chothani SP, Ramakrishnan C, Sekijima M, Gromiha MM - Biol. Direct (2015)

Structure based sequence alignment of aspartyl tRNA complexes, 1ASY, 1EFW and 1IL2. The structurally conserved regions are shown in boxes. The interacting residues are highlighted with bold letters.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4352265&req=5

Fig4: Structure based sequence alignment of aspartyl tRNA complexes, 1ASY, 1EFW and 1IL2. The structurally conserved regions are shown in boxes. The interacting residues are highlighted with bold letters.
Mentions: We have extensively studied the variation of binding site residues in different organisms for each protein-RNA complex and the normalized binding propensities of 20 amino acid residues for a typical complex, AspRS-tRNAAsp from E. coli, T. thermophilus and S. cerevisiae are shown in Table 5. We observed that the binding mode and binding site residues are distinct in these organisms. Phe prefers to be in the binding sites in E. coli whereas Gly is prefered in T. thermophilus and Pro, Met and Thr are prefered in S. cerevisiae. Although Asn, Glu and Arg show preference to be at the interface in all the organisms, the strength is different among them. The preference of Arg was higher in E. coli and T. thermophilus than Lys whereas an opposite trend was observed in S. cerevisiae. The structure based sequence alignment of AspRS from three different organisms is shown in Figure 4. We observed that the binding site residues, binding mode and binding segments are different among the three different organisms in the considered complex. The analysis of binding segments showed a similar trend at the protein level however the behavior is different in RNA among different organisms. Single nucleotide segments accommodated 67% of the binding sites in T. thermophilus whereas only 33% of the binding sites have single nucleotide segments in E. coli.Table 5

Bottom Line: We found that the proteins of mesophilic organisms have more number of binding sites than thermophiles and the binding propensities of amino acid residues are distinct in E. coli, H. sapiens, S. cerevisiae, thermophiles and archaea.Based on structural analysis and molecular dynamics simulations we suggest that the mode of recognition depends on the type of the organism in a protein-RNA complex.This article was reviewed by Sandor Pongor, Gajendra Raghava and Narayanaswamy Srinivasan.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Bhupat Jyoti Metha School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, Tamilnadu, India. nagabioinfostar@gmail.com.

ABSTRACT

Background: Protein-RNA interactions perform diverse functions within the cell. Understanding the recognition mechanism of protein-RNA complexes has been a challenging task in molecular and computational biology. In earlier works, the recognition mechanisms have been studied for a specific complex or using a set of non-redundant complexes. In this work, we have constructed 18 sets of same protein-RNA complexes belonging to different organisms from Protein Data Bank (PDB). The similarities and differences in each set of complexes have been revealed in terms of various sequence and structure based features such as root mean square deviation, sequence homology, propensity of binding site residues, variance, conservation at binding sites, binding segments, binding motifs of amino acid residues and nucleotides, preferred amino acid-nucleotide pairs and influence of neighboring residues for binding.

Results: We found that the proteins of mesophilic organisms have more number of binding sites than thermophiles and the binding propensities of amino acid residues are distinct in E. coli, H. sapiens, S. cerevisiae, thermophiles and archaea. Proteins prefer to bind with RNA using a single residue segment in all the organisms while RNA prefers to use a stretch of up to six nucleotides for binding with proteins. We have developed amino acid residue-nucleotide pair potentials for different organisms, which could be used for predicting the binding specificity. Further, molecular dynamics simulation studies on aspartyl tRNA synthetase complexed with aspartyl tRNA showed specific modes of recognition in E. coli, T. thermophilus and S. cerevisiae.

Conclusion: Based on structural analysis and molecular dynamics simulations we suggest that the mode of recognition depends on the type of the organism in a protein-RNA complex.

Reviewers: This article was reviewed by Sandor Pongor, Gajendra Raghava and Narayanaswamy Srinivasan.

No MeSH data available.


Related in: MedlinePlus