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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

Interaction with the CSDYB-1 and the position 4 of direct- (A) or reverse-oriented (B) RNA oligonucleotides (orange).A. In the direct orientation, the O2' atom of U4 forms an H-bond with the O2 atom of U3 (yellow dotted line). B. In contrast, the O4' atom of U4r does not form any H-bond, neither with other RNA atom nor with water molecule.
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pone.0130318.g008: Interaction with the CSDYB-1 and the position 4 of direct- (A) or reverse-oriented (B) RNA oligonucleotides (orange).A. In the direct orientation, the O2' atom of U4 forms an H-bond with the O2 atom of U3 (yellow dotted line). B. In contrast, the O4' atom of U4r does not form any H-bond, neither with other RNA atom nor with water molecule.

Mentions: Analysis of MDS trajectories showed that reversing the oligonucleotide orientation entails unfavorable local interactions between the oligonucleotides tested and the CSDYB-1. Although these unfavorable interactions were observed at every position on the oligonucleotide, the most striking effect was observed for the binding site N4. For instance, when the CSDYB-1 binds to an oligo(U) in direct orientation, the O2' atom of U4 establishes a stable H-bond with the O2 atom of U3 (Fig 8A). In contrast, when the binds an oligo(U) in reverse orientation (rU), the O4' atom of rU4 cannot establish any H-bond neither with atoms from neighboring nucleotides nor with water molecules (Fig 8B). Consequently, the system compensates the loss of H-bonds between the rU4r and the N4 site by interacting with water molecules. Under these conditions, the binding of oligo(U) to the CSDYB-1 is outcompeted by water molecules, which results in the dissociation of the complex and observed increasing the distance between binding sites and respective nucleotide bases. The strand specificity of the CSDYB-1:NA interaction was more prominent when the CSDYB-1 was bound to reverse oriented G-rich DNA compared with G-rich RNA. In this case, the stacking interactions were weakening more dramatically: the median distance for G-nucleotides at sites 2 was increased from 4.9Å to 7.1Å in the case of DNA and from 4.8Å to 5.2Å in the case of RNA; for the binding site 3 we observed increasing from 4.2Å to 5.2Å for DNA and similar medians of 4.3Å for RNA (Table 1). All increments were statistically significant.


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)

Interaction with the CSDYB-1 and the position 4 of direct- (A) or reverse-oriented (B) RNA oligonucleotides (orange).A. In the direct orientation, the O2' atom of U4 forms an H-bond with the O2 atom of U3 (yellow dotted line). B. In contrast, the O4' atom of U4r does not form any H-bond, neither with other RNA atom nor with water molecule.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130318.g008: Interaction with the CSDYB-1 and the position 4 of direct- (A) or reverse-oriented (B) RNA oligonucleotides (orange).A. In the direct orientation, the O2' atom of U4 forms an H-bond with the O2 atom of U3 (yellow dotted line). B. In contrast, the O4' atom of U4r does not form any H-bond, neither with other RNA atom nor with water molecule.
Mentions: Analysis of MDS trajectories showed that reversing the oligonucleotide orientation entails unfavorable local interactions between the oligonucleotides tested and the CSDYB-1. Although these unfavorable interactions were observed at every position on the oligonucleotide, the most striking effect was observed for the binding site N4. For instance, when the CSDYB-1 binds to an oligo(U) in direct orientation, the O2' atom of U4 establishes a stable H-bond with the O2 atom of U3 (Fig 8A). In contrast, when the binds an oligo(U) in reverse orientation (rU), the O4' atom of rU4 cannot establish any H-bond neither with atoms from neighboring nucleotides nor with water molecules (Fig 8B). Consequently, the system compensates the loss of H-bonds between the rU4r and the N4 site by interacting with water molecules. Under these conditions, the binding of oligo(U) to the CSDYB-1 is outcompeted by water molecules, which results in the dissociation of the complex and observed increasing the distance between binding sites and respective nucleotide bases. The strand specificity of the CSDYB-1:NA interaction was more prominent when the CSDYB-1 was bound to reverse oriented G-rich DNA compared with G-rich RNA. In this case, the stacking interactions were weakening more dramatically: the median distance for G-nucleotides at sites 2 was increased from 4.9Å to 7.1Å in the case of DNA and from 4.8Å to 5.2Å in the case of RNA; for the binding site 3 we observed increasing from 4.2Å to 5.2Å for DNA and similar medians of 4.3Å for RNA (Table 1). All increments were statistically significant.

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