Journal:Acta Cryst D:S2059798318000050

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<b>Molecular Tour</b><br>
<b>Molecular Tour</b><br>
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DNA is a structurally plastic molecule, and its biological function is enabled by adaptation to its binding partners. To identify the DNA structural polymorphisms that are possible in such adaptations, the dinucleotide structures of 60&#8197;000 DNA steps from sequentially nonredundant crystal structures were classified and an automated protocol assigning 44 distinct structural (conformational) classes called NtC (for Nucleotide Conformers) was developed.
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DNA is a structurally plastic molecule, and its biological function is enabled by adaptation to its binding partners. We identify the DNA structural polymorphisms by analyzing structures of short DNA stretches, dinucleotides. The reported paper describes in detail the analysis and the protocol of assigning distinct structural (conformational) classes called NtC (for Nucleotide Conformers) that describe the local DNA structure. To further facilitate understanding of the DNA structure, structurally similar NtC classes were grouped into 11 letters of a DNA “structural alphabet” called CANA (Conformational Alphabet of Nucleic Acids). Structural alphabet is a tool allowing to translate information about three-dimensional structure of a biopolymer into a linear sequence of letters of the alphabet simplifying thus the analysis of complex three dimensional object such as DNA in analysis of a sequence of symbols.
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To further facilitate understanding of the DNA structure, structurally similar NtC classes were grouped into 11 letters of a DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and the projection of CANA onto the graphical representation of the molecular structure was proposed. The DNA structural alphabet CANA makes the analysis of DNA structure more comprehensible yet does not compromise the impartiality of the structural description and provides a tool to characterize the DNA structure beyond a rough classification into BI-, BII-, A- and Z-DNA types. The NtC classification was further used to define a validation score called confal, which quantifies the conformity between an analyzed structure and the geometries of NtC.
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NtC, CANA and confal assignment, which is accessible at the website https://dnatco.org <ref>pmid 27150812</ref>, allows the quantitative assessment and validation of DNA structures and their subsequent analysis by means of pseudo-sequence alignment. We believe that the NtC and CANA assignment protocol will contribute to understanding DNA structures by their impartial characterization, help to refine and validate DNA crystal and NMR structures, interpret DNA molecular modelling, and facilitate challenging analyses of sequence-dependent features of DNA structures and their interactions with proteins.
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[[Image: AAA_BBB_BB2_40.png|450px|left|thumb| Gallery of the CANA letters. Each letter is represented by 40 randomly selected structures of steps which represent one NtC class belonging to the letter in the golden set. A-like and mixed B/A conformers are drawn in pink and violet, B-like conformers in blue. The CANA letter AAA is represented by NtC AA00, BBB by BB00, and BB2 by BB07.]]
[[Image: AAA_BBB_BB2_40.png|450px|left|thumb| Gallery of the CANA letters. Each letter is represented by 40 randomly selected structures of steps which represent one NtC class belonging to the letter in the golden set. A-like and mixed B/A conformers are drawn in pink and violet, B-like conformers in blue. The CANA letter AAA is represented by NtC AA00, BBB by BB00, and BB2 by BB07.]]
{{Clear}}
{{Clear}}
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Annotation of the conformational properties of a few archetypal types of DNA structures revealed some unexpected features. The Dickerson–Drew dodecamer (for example PDB entry [[1bna]]), which is often considered to be a typical B-DNA duplex, is conformationally rich, with a <scene name='77/777977/Cv/5'>high proportion of features mixing B and A forms</scene>. Our analysis of duplex models based on the fibre-diffraction data discloses the need for their critical evaluation before they are used for computer modelling. Conformational analysis of guanine quadruplexes (for example PDB entry [[1jpq]]) demonstrates the universality of the most frequent B conformer, BB00, which builds the tetrad cores of these folded DNA in combination with <scene name='77/777977/Cv/8'>more exotic conformers which have a base in syn orientation (NtC BB1S or BBS1)</scene>. A Holliday junction (for example PDB entry [[1dcw]]) is a DNA intermediate in homologous recombination. It contains four double-stranded DNA arms joined together by short links. The stems of the junctions are <scene name='77/777977/Cv/12'>usually B-DNA duplexes with very few, if any, B-A and A-B conformers</scene>. The NtC class that can be associated with the junction proper is the recurrently occurring unstacked NS04.
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The &#8764;21% of steps that are left unassigned in our procedure represent a compromise between the accuracy of the assignment and the complex nature of the DNA conformational space. A small percentage of the currently unassigned steps may subsequently be classified as new NtC classes. These classes may be quite important for understanding the detailed architecture of folded DNA, such as turns in hairpin structures or quadruplexes and still uncharacterized conformer(s) describing the i-motif fold, but they will most likely be numerically small. Undoubtedly, a fair number of the unassigned steps originate from refinement errors, but even error-free structures will have a significant number of uncharacterized conformers because of the high deformability of DNA molecules.
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NtC and CANA assignment, which is accessible at the website https://dnatco.org <ref>pmid 27150812</ref>, allows the quantitative assessment and validation of DNA structures and their subsequent analysis by means of pseudo-sequence alignment. We also proposed a projection of the CANA letters onto the graphical representation of the molecular structure that should provide a visual tool to analyze DNA structures.
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Annotation of the structural properties of a few archetypal types of DNA structures revealed some unexpected features:
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(i) The Dickerson–Drew dodecamer (for example PDB entry <scene name='77/777977/Cv/5'>1bna</scene>), which is often considered to be a typical B-DNA duplex, is conformationally rich, with a high proportion of features mixing B and A forms.
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(ii) Our analysis of duplex models based on the fibre-diffraction data discloses the need for their critical evaluation before they are used for computer modeling.
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(iii) Conformational analysis of guanine quadruplexes (for example PDB entry <scene name='77/777977/Cv/8'>1jpq</scene>) demonstrates the universality of the most frequent B conformer, BB00, which builds the tetrad cores of these folded DNA in combination with more exotic conformers which have a base in syn orientation (NtC BB1S or BBS1).
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(iv) A Holliday junction (for example PDB entry <scene name='77/777977/Cv/12'>1dcw</scene>) is a DNA intermediate in homologous recombination. It contains four double-stranded DNA arms joined together by short links. The stems of the junctions are usually B-DNA duplexes with very few, if any, B-A and A-B conformers. The NtC class that can be associated with the junction proper is the recurrently occurring unstacked NS04.
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An analysis of the DNA structures in complexes with transcription factors and with histone proteins by means of the CANA alphabet has been published <ref>doi 10.3390/genes8100278</ref> and is discussed at Proteopedia page [[Journal:Genes:1]].
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We believe that the NtC and CANA assignment protocol provides impartial characterization of the DNA structures, tools helping to refine and validate DNA crystal and NMR structures, interpret DNA molecular modeling, and facilitate challenging analyses of sequence-dependent features of DNA structures and their interactions with proteins.
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</StructureSection>
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Revision as of 08:55, 18 January 2018

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  1. ↑ Bohdan Schneider, Paulina Bozikova, Iva Necasova, Petr Cech, Daniel Svozilb and Jirı Cerný. A DNA structural alphabet provides new insight into DNA flexibility. Acta Cryst. (2018). D74, 52-64 doi:http://dx.doi.org/10.1107/S2059798318000050
  2. ↑ Cerny J, Bozikova P, Schneider B. DNATCO: assignment of DNA conformers at dnatco.org. Nucleic Acids Res. 2016 Jul 8;44(W1):W284-7. doi: 10.1093/nar/gkw381. Epub 2016, May 5. PMID:27150812 doi:http://dx.doi.org/10.1093/nar/gkw381
  3. ↑ Schneider B, Bozikova P, Cech P, Svozil D, Cerny J. A DNA Structural Alphabet Distinguishes Structural Features of DNA Bound to Regulatory Proteins and in the Nucleosome Core Particle. Genes (Basel). 2017 Oct 18;8(10). pii: genes8100278. doi: 10.3390/genes8100278. PMID:29057824 doi:http://dx.doi.org/10.3390/genes8100278

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