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DNA phosphate crowding correlates with protein cationic side chain density and helical curvature in protein/DNA crystal structures.

Grant BN, Dourlain EM, Araneda JN, Throneberry ML, McFail-Isom LA - Nucleic Acids Res. (2013)

Bottom Line: Protein-DNA complexes without significant Cpc/Cpp (36 structures) correlation (-0.25<0<0.25) tended to contain DNA without significant curvature.Interestingly, concave and convex complexes also include more arginine and lysine phosphate contacts, respectively, whereas linear complexes included essentially equivalent numbers of Lys/Arg phosphate contacts.Together, these findings suggest an important role for electrostatic interactions in protein-DNA complexes involving helical curvature.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Central Arkansas, Conway, AR 72035, USA.

ABSTRACT
Sequence-specific binding of proteins to their DNA targets involves a complex spectrum of processes that often induce DNA conformational variation in the bound complex. The forces imposed by protein binding that cause the helical deformations are intimately interrelated and difficult to parse or rank in importance. To investigate the role of electrostatics in helical deformation, we quantified the relationship between protein cationic residue density (Cpc) and DNA phosphate crowding (Cpp). The correlation between Cpc and Cpp was then calculated for a subset of 58 high resolution protein-DNA crystal structures. Those structures containing strong Cpc/Cpp correlation (>±0.25) were likely to contain DNA helical curvature. Further, the correlation factor sign predicted the direction of helical curvature with positive (16 structures) and negative (seven structures) correlation containing concave (DNA curved toward protein) and convex (DNA curved away from protein) curvature, respectively. Protein-DNA complexes without significant Cpc/Cpp (36 structures) correlation (-0.25<0<0.25) tended to contain DNA without significant curvature. Interestingly, concave and convex complexes also include more arginine and lysine phosphate contacts, respectively, whereas linear complexes included essentially equivalent numbers of Lys/Arg phosphate contacts. Together, these findings suggest an important role for electrostatic interactions in protein-DNA complexes involving helical curvature.

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Crowding function (Cpx) schematics. (a) The defining components of the Phosphate Crowding function (Cpp). For each PO, the inverse of the distances to all other POs within an 11 Å radius were summed. The 11 Å distance allowed the inclusion of the neighboring intra-strand and inter-strand POs across an average minor groove. (b) The defining components of the ion crowding function (Cpx). For each PO, the inverse distances to all charged protein side chains within the selected cut off radius were summed. The cation crowding function (Cpc) included distances between each PO and each Lys and Arg, whereas anion crowding function (Cpa) included distances between each PO and Glu and Asp (Supplementary Figure S2). Values for Cpx were calculated using increasing cut off radii (CCRx) values 1, 3, 5, 7, 9, 11, 13 and 15 Å.
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gkt492-F1: Crowding function (Cpx) schematics. (a) The defining components of the Phosphate Crowding function (Cpp). For each PO, the inverse of the distances to all other POs within an 11 Å radius were summed. The 11 Å distance allowed the inclusion of the neighboring intra-strand and inter-strand POs across an average minor groove. (b) The defining components of the ion crowding function (Cpx). For each PO, the inverse distances to all charged protein side chains within the selected cut off radius were summed. The cation crowding function (Cpc) included distances between each PO and each Lys and Arg, whereas anion crowding function (Cpa) included distances between each PO and Glu and Asp (Supplementary Figure S2). Values for Cpx were calculated using increasing cut off radii (CCRx) values 1, 3, 5, 7, 9, 11, 13 and 15 Å.

Mentions: Three crowding parameters, Cpp, Cpc and Cpa, were calculated for each PO. The phosphate crowding function value, Cpp, represents the sum of the inverse distances between a given PO and the other PO’s within the cut off radius of 11 Å (Figure 1a). This cut off radius was established based on measurements of the 1.4 Å resolution structure of the B-form DNA dodecamer (PDB 355d) (27) and chosen to include on average the PO of (1) the adjacent intra-strand phosphates and (2) the inter-strand phosphate across the narrowest span of the minor groove. The phosphate crowding function will include additional POs if DNA deformation induces phosphate crowding, placing those POs within the radius.Figure 1.


DNA phosphate crowding correlates with protein cationic side chain density and helical curvature in protein/DNA crystal structures.

Grant BN, Dourlain EM, Araneda JN, Throneberry ML, McFail-Isom LA - Nucleic Acids Res. (2013)

Crowding function (Cpx) schematics. (a) The defining components of the Phosphate Crowding function (Cpp). For each PO, the inverse of the distances to all other POs within an 11 Å radius were summed. The 11 Å distance allowed the inclusion of the neighboring intra-strand and inter-strand POs across an average minor groove. (b) The defining components of the ion crowding function (Cpx). For each PO, the inverse distances to all charged protein side chains within the selected cut off radius were summed. The cation crowding function (Cpc) included distances between each PO and each Lys and Arg, whereas anion crowding function (Cpa) included distances between each PO and Glu and Asp (Supplementary Figure S2). Values for Cpx were calculated using increasing cut off radii (CCRx) values 1, 3, 5, 7, 9, 11, 13 and 15 Å.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3753625&req=5

gkt492-F1: Crowding function (Cpx) schematics. (a) The defining components of the Phosphate Crowding function (Cpp). For each PO, the inverse of the distances to all other POs within an 11 Å radius were summed. The 11 Å distance allowed the inclusion of the neighboring intra-strand and inter-strand POs across an average minor groove. (b) The defining components of the ion crowding function (Cpx). For each PO, the inverse distances to all charged protein side chains within the selected cut off radius were summed. The cation crowding function (Cpc) included distances between each PO and each Lys and Arg, whereas anion crowding function (Cpa) included distances between each PO and Glu and Asp (Supplementary Figure S2). Values for Cpx were calculated using increasing cut off radii (CCRx) values 1, 3, 5, 7, 9, 11, 13 and 15 Å.
Mentions: Three crowding parameters, Cpp, Cpc and Cpa, were calculated for each PO. The phosphate crowding function value, Cpp, represents the sum of the inverse distances between a given PO and the other PO’s within the cut off radius of 11 Å (Figure 1a). This cut off radius was established based on measurements of the 1.4 Å resolution structure of the B-form DNA dodecamer (PDB 355d) (27) and chosen to include on average the PO of (1) the adjacent intra-strand phosphates and (2) the inter-strand phosphate across the narrowest span of the minor groove. The phosphate crowding function will include additional POs if DNA deformation induces phosphate crowding, placing those POs within the radius.Figure 1.

Bottom Line: Protein-DNA complexes without significant Cpc/Cpp (36 structures) correlation (-0.25<0<0.25) tended to contain DNA without significant curvature.Interestingly, concave and convex complexes also include more arginine and lysine phosphate contacts, respectively, whereas linear complexes included essentially equivalent numbers of Lys/Arg phosphate contacts.Together, these findings suggest an important role for electrostatic interactions in protein-DNA complexes involving helical curvature.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Central Arkansas, Conway, AR 72035, USA.

ABSTRACT
Sequence-specific binding of proteins to their DNA targets involves a complex spectrum of processes that often induce DNA conformational variation in the bound complex. The forces imposed by protein binding that cause the helical deformations are intimately interrelated and difficult to parse or rank in importance. To investigate the role of electrostatics in helical deformation, we quantified the relationship between protein cationic residue density (Cpc) and DNA phosphate crowding (Cpp). The correlation between Cpc and Cpp was then calculated for a subset of 58 high resolution protein-DNA crystal structures. Those structures containing strong Cpc/Cpp correlation (>±0.25) were likely to contain DNA helical curvature. Further, the correlation factor sign predicted the direction of helical curvature with positive (16 structures) and negative (seven structures) correlation containing concave (DNA curved toward protein) and convex (DNA curved away from protein) curvature, respectively. Protein-DNA complexes without significant Cpc/Cpp (36 structures) correlation (-0.25<0<0.25) tended to contain DNA without significant curvature. Interestingly, concave and convex complexes also include more arginine and lysine phosphate contacts, respectively, whereas linear complexes included essentially equivalent numbers of Lys/Arg phosphate contacts. Together, these findings suggest an important role for electrostatic interactions in protein-DNA complexes involving helical curvature.

Show MeSH
Related in: MedlinePlus