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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

The CSDYB-1 preferentially binds to GGT sequence.A. Binding of the CSDYB-1 to oligo(dG) at positions 2 and 3 involves the formation intermolecular H-bonds (yellow dotted lines), including specific H-bonds between G2 and Glu71. In addition, specific intramolecular H-bonds (red dotted lines) between G2 and G3 were also observed. B. Binding of the CSDYB-1 to oligo(dT) at position 4 involves stacking interaction with Phe24 and the formation intermolecular H-bonds (yellow dotted lines) with Asp33 and Lys14. In addition, the interaction of oligo(dT) and the CSDYB-1 promotes the formation of an intramolecular H-bond between Asp33 and Lys14 (red dotted line).
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pone.0130318.g004: The CSDYB-1 preferentially binds to GGT sequence.A. Binding of the CSDYB-1 to oligo(dG) at positions 2 and 3 involves the formation intermolecular H-bonds (yellow dotted lines), including specific H-bonds between G2 and Glu71. In addition, specific intramolecular H-bonds (red dotted lines) between G2 and G3 were also observed. B. Binding of the CSDYB-1 to oligo(dT) at position 4 involves stacking interaction with Phe24 and the formation intermolecular H-bonds (yellow dotted lines) with Asp33 and Lys14. In addition, the interaction of oligo(dT) and the CSDYB-1 promotes the formation of an intramolecular H-bond between Asp33 and Lys14 (red dotted line).

Mentions: Contrary to the CSDYB-1, bacterial CSPs exhibit a higher affinity for T-rich sequences [26,27]. The present results show that this specificity is mainly determined by the NH group of Lys39 main chain and the NE2 atom of Gln59 side chain of Bs-CSP, which form strong H-bonds with the O4 and O2 atoms of thymidine at the N1 and N2 sites, respectively (Fig 2A). In the CSDYB-1, the N1 site is absent, and Gln59 is substituted by Glu71 at the N2 site. This Gln to Glu substitution at the N2 site completely changes the specificity of the CSDYB-1 where only a guanine can bind strongly and specifically at this position. This interaction is favored by the formation of strong H-bonds between the side chain of Glu71 and the nitrogen atoms N1 and N2 of dG2 (Fig 4A). These H-bonds had an average occupancy > 60%, which was also accompanied by a lower solvent accessibility of the respective atoms, strengthening these interactions. In addition, the formation of transient H-bonds between dG2 and dG3 was observed along the simulation (average occupancy of 25% over the 3 trajectory replicates) which may favor the binding of a guanine at the position N2.


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)

The CSDYB-1 preferentially binds to GGT sequence.A. Binding of the CSDYB-1 to oligo(dG) at positions 2 and 3 involves the formation intermolecular H-bonds (yellow dotted lines), including specific H-bonds between G2 and Glu71. In addition, specific intramolecular H-bonds (red dotted lines) between G2 and G3 were also observed. B. Binding of the CSDYB-1 to oligo(dT) at position 4 involves stacking interaction with Phe24 and the formation intermolecular H-bonds (yellow dotted lines) with Asp33 and Lys14. In addition, the interaction of oligo(dT) and the CSDYB-1 promotes the formation of an intramolecular H-bond between Asp33 and Lys14 (red dotted line).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130318.g004: The CSDYB-1 preferentially binds to GGT sequence.A. Binding of the CSDYB-1 to oligo(dG) at positions 2 and 3 involves the formation intermolecular H-bonds (yellow dotted lines), including specific H-bonds between G2 and Glu71. In addition, specific intramolecular H-bonds (red dotted lines) between G2 and G3 were also observed. B. Binding of the CSDYB-1 to oligo(dT) at position 4 involves stacking interaction with Phe24 and the formation intermolecular H-bonds (yellow dotted lines) with Asp33 and Lys14. In addition, the interaction of oligo(dT) and the CSDYB-1 promotes the formation of an intramolecular H-bond between Asp33 and Lys14 (red dotted line).
Mentions: Contrary to the CSDYB-1, bacterial CSPs exhibit a higher affinity for T-rich sequences [26,27]. The present results show that this specificity is mainly determined by the NH group of Lys39 main chain and the NE2 atom of Gln59 side chain of Bs-CSP, which form strong H-bonds with the O4 and O2 atoms of thymidine at the N1 and N2 sites, respectively (Fig 2A). In the CSDYB-1, the N1 site is absent, and Gln59 is substituted by Glu71 at the N2 site. This Gln to Glu substitution at the N2 site completely changes the specificity of the CSDYB-1 where only a guanine can bind strongly and specifically at this position. This interaction is favored by the formation of strong H-bonds between the side chain of Glu71 and the nitrogen atoms N1 and N2 of dG2 (Fig 4A). These H-bonds had an average occupancy > 60%, which was also accompanied by a lower solvent accessibility of the respective atoms, strengthening these interactions. In addition, the formation of transient H-bonds between dG2 and dG3 was observed along the simulation (average occupancy of 25% over the 3 trajectory replicates) which may favor the binding of a guanine at the position N2.

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