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The Cold Shock Domain of YB-1 Segregates RNA from DNA by Non-Bonded Interactions.

Kljashtorny V, Nikonov S, Ovchinnikov L, Lyabin D, Vodovar N, Curmi P, Manivet P - PLoS ONE (2015)

Bottom Line: Using molecular dynamics simulation approaches validated by experimental assays, the YB1 CSD was found to interact with nucleic acids in a sequence-dependent manner and with a higher affinity for RNA than DNA.The binding properties of the YB1 CSD were close to those observed for the related bacterial Cold Shock Proteins (CSP), albeit some differences in sequence specificity.The results provide insights in the molecular mechanisms whereby YB-1 interacts with nucleic acids.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia; Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 829, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Bd François Mitterrand, 91025 Evry Cedex, France; Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 942, Hôpital Lariboisière, 41 boulevard de la Chapelle, 75475 Paris cedex 10, France; Assistance Publique-Hôpitaux de paris (APHP), Hôpital Lariboisière, Service de Biochimie et de Biologie Moléculaire, Paris, France.

ABSTRACT
The human YB-1 protein plays multiple cellular roles, of which many are dictated by its binding to RNA and DNA through its Cold Shock Domain (CSD). Using molecular dynamics simulation approaches validated by experimental assays, the YB1 CSD was found to interact with nucleic acids in a sequence-dependent manner and with a higher affinity for RNA than DNA. The binding properties of the YB1 CSD were close to those observed for the related bacterial Cold Shock Proteins (CSP), albeit some differences in sequence specificity. The results provide insights in the molecular mechanisms whereby YB-1 interacts with nucleic acids.

No MeSH data available.


Related in: MedlinePlus

Number of intermolecular H-bonds in the complexes of CSD with different desoxyribooligonucleotides.
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pone.0130318.g003: Number of intermolecular H-bonds in the complexes of CSD with different desoxyribooligonucleotides.

Mentions: In contrast, the CSDYB-1:oligoT and the CSDYB-1:oligoC complexes were found significantly less stable with median distances between bases and CSD aromatic residues > 7 Å with only exception of dT at site N2 (distance = 4.8Å, angle = 26°). In particular, in the CSDYB-1:oligo(dC) complex, initial contacts at key positions were lost within the first nanoseconds of the MDS although non-specific interactions prevented the complex to dissociate. All the complexes with oligo(dA), oligo(dT), oligo(dC) had much higher ΔGbind values compared with oligo(dG) which was driven not only by weaker stacking interactions but also by a total number of intermolecular hydrogen bonds. Thus, the average number of H-bonds between CSD and oligo(dG) was 7.1 whereas in the other complexes this number varied from 5.0 to 5.4 (Fig 3). The t-tests for the mean comparisons for the number of intermolecular H-bonds between different complexes revealed the statistically significant difference between all the groups (P-value < 0.001). However the difference was only biologically meaningful when compared CSDYB-1:oligo(dG) with other complexes. The Cohen’s D value [45] for these comparisons ranged between 0.8 and 1 standard deviation with absolute difference of about 2 H-bonds. Such a difference could correspond to a two-folds increase in affinity of CSDYB-1 for oligo(dG) compared to other oligonucleotides. Among other oligonucleotides oligo(dA) seems to be slightly more preferable ligand for CSDYB-1 followed by oligo(dT).


The Cold Shock Domain of YB-1 Segregates RNA from DNA by Non-Bonded Interactions.

Kljashtorny V, Nikonov S, Ovchinnikov L, Lyabin D, Vodovar N, Curmi P, Manivet P - PLoS ONE (2015)

Number of intermolecular H-bonds in the complexes of CSD with different desoxyribooligonucleotides.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493011&req=5

pone.0130318.g003: Number of intermolecular H-bonds in the complexes of CSD with different desoxyribooligonucleotides.
Mentions: In contrast, the CSDYB-1:oligoT and the CSDYB-1:oligoC complexes were found significantly less stable with median distances between bases and CSD aromatic residues > 7 Å with only exception of dT at site N2 (distance = 4.8Å, angle = 26°). In particular, in the CSDYB-1:oligo(dC) complex, initial contacts at key positions were lost within the first nanoseconds of the MDS although non-specific interactions prevented the complex to dissociate. All the complexes with oligo(dA), oligo(dT), oligo(dC) had much higher ΔGbind values compared with oligo(dG) which was driven not only by weaker stacking interactions but also by a total number of intermolecular hydrogen bonds. Thus, the average number of H-bonds between CSD and oligo(dG) was 7.1 whereas in the other complexes this number varied from 5.0 to 5.4 (Fig 3). The t-tests for the mean comparisons for the number of intermolecular H-bonds between different complexes revealed the statistically significant difference between all the groups (P-value < 0.001). However the difference was only biologically meaningful when compared CSDYB-1:oligo(dG) with other complexes. The Cohen’s D value [45] for these comparisons ranged between 0.8 and 1 standard deviation with absolute difference of about 2 H-bonds. Such a difference could correspond to a two-folds increase in affinity of CSDYB-1 for oligo(dG) compared to other oligonucleotides. Among other oligonucleotides oligo(dA) seems to be slightly more preferable ligand for CSDYB-1 followed by oligo(dT).

Bottom Line: Using molecular dynamics simulation approaches validated by experimental assays, the YB1 CSD was found to interact with nucleic acids in a sequence-dependent manner and with a higher affinity for RNA than DNA.The binding properties of the YB1 CSD were close to those observed for the related bacterial Cold Shock Proteins (CSP), albeit some differences in sequence specificity.The results provide insights in the molecular mechanisms whereby YB-1 interacts with nucleic acids.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia; Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 829, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Bd François Mitterrand, 91025 Evry Cedex, France; Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 942, Hôpital Lariboisière, 41 boulevard de la Chapelle, 75475 Paris cedex 10, France; Assistance Publique-Hôpitaux de paris (APHP), Hôpital Lariboisière, Service de Biochimie et de Biologie Moléculaire, Paris, France.

ABSTRACT
The human YB-1 protein plays multiple cellular roles, of which many are dictated by its binding to RNA and DNA through its Cold Shock Domain (CSD). Using molecular dynamics simulation approaches validated by experimental assays, the YB1 CSD was found to interact with nucleic acids in a sequence-dependent manner and with a higher affinity for RNA than DNA. The binding properties of the YB1 CSD were close to those observed for the related bacterial Cold Shock Proteins (CSP), albeit some differences in sequence specificity. The results provide insights in the molecular mechanisms whereby YB-1 interacts with nucleic acids.

No MeSH data available.


Related in: MedlinePlus