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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 binds preferentially to direct-oriented RNA.A. RNA-binding on the surface of CSD (grey) bound to an oligo(U) (green). Intramolecular H-bonds formed between ribonucleotides (yellow dotted lines) stabilise the local conformation of RNA when bound to the CSD. The CSD is shown in grey, the backbone of the oligonucleotide is shown in orange and the bases are shown in green. Nucleotides numbering is indicated. This H-bond network is not formed within DNA molecules. B and C. Planar representation of the interaction between CSD and direct- (B) or reverse-oriented (C) oligoribonucleotides. Regardless the orientation of the oligonucleotide, intermolecular H-bonding (green lines) between amino acids and ribonucleotides is identical, with the exception of the H-bond formed between His37 and U2 only observed for direct oligo(U) (B). The binding of the CSDYB-1 to a direct-oriented oligo(U) promotes the formation of intra-oligonucleotide H-bonding (red dashed line) that stabilises the interaction (B, H-bonds correspond to A). However, this intramolecular network is not formed when CSD binds to the reverse-oriented oligonucleotide (C) Consequently, this interaction is less favourable as illustrated by the weakening of the stacking (blue arrow) interaction between amino acids and nucleotides at positions 2 and 3 (marked with X).
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pone.0130318.g006: The CSDYB-1 binds preferentially to direct-oriented RNA.A. RNA-binding on the surface of CSD (grey) bound to an oligo(U) (green). Intramolecular H-bonds formed between ribonucleotides (yellow dotted lines) stabilise the local conformation of RNA when bound to the CSD. The CSD is shown in grey, the backbone of the oligonucleotide is shown in orange and the bases are shown in green. Nucleotides numbering is indicated. This H-bond network is not formed within DNA molecules. B and C. Planar representation of the interaction between CSD and direct- (B) or reverse-oriented (C) oligoribonucleotides. Regardless the orientation of the oligonucleotide, intermolecular H-bonding (green lines) between amino acids and ribonucleotides is identical, with the exception of the H-bond formed between His37 and U2 only observed for direct oligo(U) (B). The binding of the CSDYB-1 to a direct-oriented oligo(U) promotes the formation of intra-oligonucleotide H-bonding (red dashed line) that stabilises the interaction (B, H-bonds correspond to A). However, this intramolecular network is not formed when CSD binds to the reverse-oriented oligonucleotide (C) Consequently, this interaction is less favourable as illustrated by the weakening of the stacking (blue arrow) interaction between amino acids and nucleotides at positions 2 and 3 (marked with X).

Mentions: The CSDYB-1:oligo(G) interaction was found more stable when compared to the CSDYB-1:oligo(dG) interaction (S2 Table). Deoxyribonucleotides differ from ribonucleotides by the lack of an alcohol group at the position 2' of the ribose. We found that this extra-OH groups present in RNA molecules were involved in both CSDYB-1:RNA and intra-RNA interactions that were obviously not observed for DNA. In particular, several stable H-bonds were observed between the CSDYB-1 residues Asn17, Tyr22, Gln38, Glu65, Gly66 and Lys68 and the ribose atoms at position 0, 1, 5, 6 and 8 (S3 Table). In addition, specific RNA intra-molecular H-bonds that involved the 2'-OH groups of the ribose of nucleotides 2 to 5 were detected (Fig 6A). These RNA-specific bonds should directly contribute to the higher affinity of the CSDYB-1 to RNA compared to DNA.


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 binds preferentially to direct-oriented RNA.A. RNA-binding on the surface of CSD (grey) bound to an oligo(U) (green). Intramolecular H-bonds formed between ribonucleotides (yellow dotted lines) stabilise the local conformation of RNA when bound to the CSD. The CSD is shown in grey, the backbone of the oligonucleotide is shown in orange and the bases are shown in green. Nucleotides numbering is indicated. This H-bond network is not formed within DNA molecules. B and C. Planar representation of the interaction between CSD and direct- (B) or reverse-oriented (C) oligoribonucleotides. Regardless the orientation of the oligonucleotide, intermolecular H-bonding (green lines) between amino acids and ribonucleotides is identical, with the exception of the H-bond formed between His37 and U2 only observed for direct oligo(U) (B). The binding of the CSDYB-1 to a direct-oriented oligo(U) promotes the formation of intra-oligonucleotide H-bonding (red dashed line) that stabilises the interaction (B, H-bonds correspond to A). However, this intramolecular network is not formed when CSD binds to the reverse-oriented oligonucleotide (C) Consequently, this interaction is less favourable as illustrated by the weakening of the stacking (blue arrow) interaction between amino acids and nucleotides at positions 2 and 3 (marked with X).
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Related In: Results  -  Collection

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

pone.0130318.g006: The CSDYB-1 binds preferentially to direct-oriented RNA.A. RNA-binding on the surface of CSD (grey) bound to an oligo(U) (green). Intramolecular H-bonds formed between ribonucleotides (yellow dotted lines) stabilise the local conformation of RNA when bound to the CSD. The CSD is shown in grey, the backbone of the oligonucleotide is shown in orange and the bases are shown in green. Nucleotides numbering is indicated. This H-bond network is not formed within DNA molecules. B and C. Planar representation of the interaction between CSD and direct- (B) or reverse-oriented (C) oligoribonucleotides. Regardless the orientation of the oligonucleotide, intermolecular H-bonding (green lines) between amino acids and ribonucleotides is identical, with the exception of the H-bond formed between His37 and U2 only observed for direct oligo(U) (B). The binding of the CSDYB-1 to a direct-oriented oligo(U) promotes the formation of intra-oligonucleotide H-bonding (red dashed line) that stabilises the interaction (B, H-bonds correspond to A). However, this intramolecular network is not formed when CSD binds to the reverse-oriented oligonucleotide (C) Consequently, this interaction is less favourable as illustrated by the weakening of the stacking (blue arrow) interaction between amino acids and nucleotides at positions 2 and 3 (marked with X).
Mentions: The CSDYB-1:oligo(G) interaction was found more stable when compared to the CSDYB-1:oligo(dG) interaction (S2 Table). Deoxyribonucleotides differ from ribonucleotides by the lack of an alcohol group at the position 2' of the ribose. We found that this extra-OH groups present in RNA molecules were involved in both CSDYB-1:RNA and intra-RNA interactions that were obviously not observed for DNA. In particular, several stable H-bonds were observed between the CSDYB-1 residues Asn17, Tyr22, Gln38, Glu65, Gly66 and Lys68 and the ribose atoms at position 0, 1, 5, 6 and 8 (S3 Table). In addition, specific RNA intra-molecular H-bonds that involved the 2'-OH groups of the ribose of nucleotides 2 to 5 were detected (Fig 6A). These RNA-specific bonds should directly contribute to the higher affinity of the CSDYB-1 to RNA compared to DNA.

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