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New insights into Hoogsteen base pairs in DNA duplexes from a structure-based survey.

Zhou H, Hintze BJ, Kimsey IJ, Sathyamoorthy B, Yang S, Richardson JS, Al-Hashimi HM - Nucleic Acids Res. (2015)

Bottom Line: The survey identifies 106 A•T and 34 G•C HG bps in DNA duplexes, many of which are undocumented in the literature.The survey reveals HG preferences similar to those observed for transient HG bps in solution by nuclear magnetic resonance, including stronger preferences for A•T versus G•C bps, TA versus GG steps, and also suggests enrichment at terminal ends with a preference for 5'-purine.The survey provides insights into the preferences and structural consequences of HG bps in duplex DNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Duke University, Durham, NC 27710, USA.

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Global DNA bending about HG bps (A) Definition of H1 and H2 in HG bp containing DNA duplexes used to compute inter-helical Euler angles. (B) Reference frame used to define the inter-helical Euler angles (αh, βh, γh) of the target helix along with a reference idealized B-form DNA helix consisting of lower (iH1, in green) and upper (iH2, in gray) helices. The lower helix (H1, in green) of the target helix is superimposed onto iH1. (C) Definition of the rotation axis around the Z direction for the calculation of inter-helical Euler angles. The C1′–C1′ vector of the WC bp of iH1 nearest to iH2 is oriented along the y-axis. This orientation makes it possible to distinguish bending toward major or minor groove by the value of γh. (D) Examples of DNA bending at single (PDBID: 1K61) and tandem HG bps (PDBID: 3KZ8) in DNA–protein complexes. Structures are overlaid on reference B-form DNA helix (in gray). (E) Correlation plot between the inter-helical bend angle (βh) and corresponding C1′–C1′ distance across the HG or HG-like bp. (F) The bending directions (γh) of nine structures containing helical HG and HG-like bps (in red) compared to those of 11 linear control B-form DNA structures (in gray).
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Figure 5: Global DNA bending about HG bps (A) Definition of H1 and H2 in HG bp containing DNA duplexes used to compute inter-helical Euler angles. (B) Reference frame used to define the inter-helical Euler angles (αh, βh, γh) of the target helix along with a reference idealized B-form DNA helix consisting of lower (iH1, in green) and upper (iH2, in gray) helices. The lower helix (H1, in green) of the target helix is superimposed onto iH1. (C) Definition of the rotation axis around the Z direction for the calculation of inter-helical Euler angles. The C1′–C1′ vector of the WC bp of iH1 nearest to iH2 is oriented along the y-axis. This orientation makes it possible to distinguish bending toward major or minor groove by the value of γh. (D) Examples of DNA bending at single (PDBID: 1K61) and tandem HG bps (PDBID: 3KZ8) in DNA–protein complexes. Structures are overlaid on reference B-form DNA helix (in gray). (E) Correlation plot between the inter-helical bend angle (βh) and corresponding C1′–C1′ distance across the HG or HG-like bp. (F) The bending directions (γh) of nine structures containing helical HG and HG-like bps (in red) compared to those of 11 linear control B-form DNA structures (in gray).

Mentions: To assess the impact of HG bps on the DNA structure, we adopted the inter-helical Euler angle protocol developed for describing relative orientations of RNA A-form helices across junctions (59,60). Here, three inter-helical Euler angles (αh, βh, γh) are computed which describe the relative orientation of two helices across a given junction, in this case, a single or tandem HG/HG-like bps. For a given target DNA structure containing HG bps, we define a corresponding lower helix H1 and upper helix H2 to be the helices at the 5′ and 3′ sides, respectively, of the syn purine base in an HG bp (see Figure 5A). The inter-helical Euler angles describe the orientation of H2 relative to H1 across the junction of HG/HG-like bps and are determined by computing the rotation matrix that is required in order to rotate H2 so that it is in perfect coaxial alignment with H1. The approach has been described elsewhere in A-form RNA (59–61). Here we provide a brief description emphasizing those differences that relate to bending in B-form DNA. βh is the inter-helical bend angle between H2 and H1, and ranges between 0° and 180°. αh and γh are defined as ‘twist’ and ‘arc’ angles of H2 around the H2 and H1 helical axes, respectively, and range between −180° and 180° (see Figure 5B). The inter-helical Euler angles (αh, βh, γh) are computed relative to a reference idealized B-form linear helix with 10 bps per turn consisting of two consecutive and perfectly coaxial helices (iH1 and iH2). This reference B-form helix was constructed using the 3DNA fiber model (62) and the helix axis was oriented along the z-axis (see Figure 5B). The C1′–C1′ vector across the WC bp in iH1 immediately neighboring the junction was oriented along the y-axis with the major groove facing the +x direction (see Figure 5C). H1 in the target DNA structure was superimposed onto iH1 using heavy atoms (i.e. C, N, O, P) in the sugar-phosphodiester backbone. Next, reference helix iH2 was superimposed onto the resulting target helix H2 to yield iH2′. A rotation matrix R(αh, βh, γh) was then computed to transform iH2′ back to iH2 using the EULER-RNA program (https://sites.google.com/site/hashimigroup/resources) (60,63). The direct output (αh0, βh0, γh0) from EULER-RNA was then converted based on the current definition of inter-helical Euler angles by\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{upgreek}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}}{}\begin{equation*} \begin{array}{*{20}l} {if\beta _h^0 \ge 0,(\alpha _h ,\beta _h ,\gamma _h ) = (\alpha _h^0 ,\beta _h^0 ,\gamma _h^0 );} \\ {if\beta _h^0 < 0,(\alpha _h ,\beta _h ,\gamma _h ) = (\alpha _h^0 \pm 180^\circ , - \beta _h^0 ,\gamma _h^0 \pm 180^\circ )} \\ \end{array} \end{equation*}\end{document}


New insights into Hoogsteen base pairs in DNA duplexes from a structure-based survey.

Zhou H, Hintze BJ, Kimsey IJ, Sathyamoorthy B, Yang S, Richardson JS, Al-Hashimi HM - Nucleic Acids Res. (2015)

Global DNA bending about HG bps (A) Definition of H1 and H2 in HG bp containing DNA duplexes used to compute inter-helical Euler angles. (B) Reference frame used to define the inter-helical Euler angles (αh, βh, γh) of the target helix along with a reference idealized B-form DNA helix consisting of lower (iH1, in green) and upper (iH2, in gray) helices. The lower helix (H1, in green) of the target helix is superimposed onto iH1. (C) Definition of the rotation axis around the Z direction for the calculation of inter-helical Euler angles. The C1′–C1′ vector of the WC bp of iH1 nearest to iH2 is oriented along the y-axis. This orientation makes it possible to distinguish bending toward major or minor groove by the value of γh. (D) Examples of DNA bending at single (PDBID: 1K61) and tandem HG bps (PDBID: 3KZ8) in DNA–protein complexes. Structures are overlaid on reference B-form DNA helix (in gray). (E) Correlation plot between the inter-helical bend angle (βh) and corresponding C1′–C1′ distance across the HG or HG-like bp. (F) The bending directions (γh) of nine structures containing helical HG and HG-like bps (in red) compared to those of 11 linear control B-form DNA structures (in gray).
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Figure 5: Global DNA bending about HG bps (A) Definition of H1 and H2 in HG bp containing DNA duplexes used to compute inter-helical Euler angles. (B) Reference frame used to define the inter-helical Euler angles (αh, βh, γh) of the target helix along with a reference idealized B-form DNA helix consisting of lower (iH1, in green) and upper (iH2, in gray) helices. The lower helix (H1, in green) of the target helix is superimposed onto iH1. (C) Definition of the rotation axis around the Z direction for the calculation of inter-helical Euler angles. The C1′–C1′ vector of the WC bp of iH1 nearest to iH2 is oriented along the y-axis. This orientation makes it possible to distinguish bending toward major or minor groove by the value of γh. (D) Examples of DNA bending at single (PDBID: 1K61) and tandem HG bps (PDBID: 3KZ8) in DNA–protein complexes. Structures are overlaid on reference B-form DNA helix (in gray). (E) Correlation plot between the inter-helical bend angle (βh) and corresponding C1′–C1′ distance across the HG or HG-like bp. (F) The bending directions (γh) of nine structures containing helical HG and HG-like bps (in red) compared to those of 11 linear control B-form DNA structures (in gray).
Mentions: To assess the impact of HG bps on the DNA structure, we adopted the inter-helical Euler angle protocol developed for describing relative orientations of RNA A-form helices across junctions (59,60). Here, three inter-helical Euler angles (αh, βh, γh) are computed which describe the relative orientation of two helices across a given junction, in this case, a single or tandem HG/HG-like bps. For a given target DNA structure containing HG bps, we define a corresponding lower helix H1 and upper helix H2 to be the helices at the 5′ and 3′ sides, respectively, of the syn purine base in an HG bp (see Figure 5A). The inter-helical Euler angles describe the orientation of H2 relative to H1 across the junction of HG/HG-like bps and are determined by computing the rotation matrix that is required in order to rotate H2 so that it is in perfect coaxial alignment with H1. The approach has been described elsewhere in A-form RNA (59–61). Here we provide a brief description emphasizing those differences that relate to bending in B-form DNA. βh is the inter-helical bend angle between H2 and H1, and ranges between 0° and 180°. αh and γh are defined as ‘twist’ and ‘arc’ angles of H2 around the H2 and H1 helical axes, respectively, and range between −180° and 180° (see Figure 5B). The inter-helical Euler angles (αh, βh, γh) are computed relative to a reference idealized B-form linear helix with 10 bps per turn consisting of two consecutive and perfectly coaxial helices (iH1 and iH2). This reference B-form helix was constructed using the 3DNA fiber model (62) and the helix axis was oriented along the z-axis (see Figure 5B). The C1′–C1′ vector across the WC bp in iH1 immediately neighboring the junction was oriented along the y-axis with the major groove facing the +x direction (see Figure 5C). H1 in the target DNA structure was superimposed onto iH1 using heavy atoms (i.e. C, N, O, P) in the sugar-phosphodiester backbone. Next, reference helix iH2 was superimposed onto the resulting target helix H2 to yield iH2′. A rotation matrix R(αh, βh, γh) was then computed to transform iH2′ back to iH2 using the EULER-RNA program (https://sites.google.com/site/hashimigroup/resources) (60,63). The direct output (αh0, βh0, γh0) from EULER-RNA was then converted based on the current definition of inter-helical Euler angles by\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{upgreek}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}}{}\begin{equation*} \begin{array}{*{20}l} {if\beta _h^0 \ge 0,(\alpha _h ,\beta _h ,\gamma _h ) = (\alpha _h^0 ,\beta _h^0 ,\gamma _h^0 );} \\ {if\beta _h^0 < 0,(\alpha _h ,\beta _h ,\gamma _h ) = (\alpha _h^0 \pm 180^\circ , - \beta _h^0 ,\gamma _h^0 \pm 180^\circ )} \\ \end{array} \end{equation*}\end{document}

Bottom Line: The survey identifies 106 A•T and 34 G•C HG bps in DNA duplexes, many of which are undocumented in the literature.The survey reveals HG preferences similar to those observed for transient HG bps in solution by nuclear magnetic resonance, including stronger preferences for A•T versus G•C bps, TA versus GG steps, and also suggests enrichment at terminal ends with a preference for 5'-purine.The survey provides insights into the preferences and structural consequences of HG bps in duplex DNA.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Duke University, Durham, NC 27710, USA.

Show MeSH
Related in: MedlinePlus