Limits...
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

Sequence alignment of the CSDs from eukaryotic Y-box proteins and prokaryotic CSPs.A. The RNA-binding motifs are boxed in red; highly conserved amino acid residues (identity > 95%) are highlighted in black. B. 3D representation of the human CSDYB-1 structure. The RNP-1 and RNP-2 motifs are shown in yellow; N and C indicate the N- and C-termini of the domain.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493011&req=5

pone.0130318.g001: Sequence alignment of the CSDs from eukaryotic Y-box proteins and prokaryotic CSPs.A. The RNA-binding motifs are boxed in red; highly conserved amino acid residues (identity > 95%) are highlighted in black. B. 3D representation of the human CSDYB-1 structure. The RNP-1 and RNP-2 motifs are shown in yellow; N and C indicate the N- and C-termini of the domain.

Mentions: YB-1 contains three domains: a N-terminal alanine/proline rich domain (A/P), an intermediate Cold Shock Domain (CSD) which comprises two RNA-binding motifs RNP-1 and RNP-2 that are conserved among eukaryotic YB-1 proteins and prokaryotic CSD proteins (CSP, Fig 1A), and a C-terminal domain which contains alternating positively and negatively charged amino-acid clusters. YB-1 is a rather difficult target for both NMR and X-ray structural methods due to its intrinsic instability that has hampered the solving of its overall structure so far. The only structural information available to date is the NMR structure of the CSD from human YB-1 (named hereafter CSDYB-1) [22]. The CSDYB-1 exhibits a highly conserved beta-barrel structure (Fig 1B), which has been described in many nucleic acids binding proteins [23]. Interestingly, bacterial CSPs consist of a single cold shock domain and are involved to low temperature adaptation [24].


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)

Sequence alignment of the CSDs from eukaryotic Y-box proteins and prokaryotic CSPs.A. The RNA-binding motifs are boxed in red; highly conserved amino acid residues (identity > 95%) are highlighted in black. B. 3D representation of the human CSDYB-1 structure. The RNP-1 and RNP-2 motifs are shown in yellow; N and C indicate the N- and C-termini of the domain.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130318.g001: Sequence alignment of the CSDs from eukaryotic Y-box proteins and prokaryotic CSPs.A. The RNA-binding motifs are boxed in red; highly conserved amino acid residues (identity > 95%) are highlighted in black. B. 3D representation of the human CSDYB-1 structure. The RNP-1 and RNP-2 motifs are shown in yellow; N and C indicate the N- and C-termini of the domain.
Mentions: YB-1 contains three domains: a N-terminal alanine/proline rich domain (A/P), an intermediate Cold Shock Domain (CSD) which comprises two RNA-binding motifs RNP-1 and RNP-2 that are conserved among eukaryotic YB-1 proteins and prokaryotic CSD proteins (CSP, Fig 1A), and a C-terminal domain which contains alternating positively and negatively charged amino-acid clusters. YB-1 is a rather difficult target for both NMR and X-ray structural methods due to its intrinsic instability that has hampered the solving of its overall structure so far. The only structural information available to date is the NMR structure of the CSD from human YB-1 (named hereafter CSDYB-1) [22]. The CSDYB-1 exhibits a highly conserved beta-barrel structure (Fig 1B), which has been described in many nucleic acids binding proteins [23]. Interestingly, bacterial CSPs consist of a single cold shock domain and are involved to low temperature adaptation [24].

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