Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing
Identifieur interne : 000F41 ( Pmc/Curation ); précédent : 000F40; suivant : 000F42Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing
Auteurs : Pradeep S. Pallan [États-Unis] ; Paolo Lubini ; Martin Bolli [Suisse] ; Martin Egli [États-Unis]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2007.
Abstract
The crystal structure of the duplex formed by oligo(2′,3′-dideoxy-
Url:
DOI: 10.1093/nar/gkm612
PubMed: 17905816
PubMed Central: 2095819
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Paolo Lubini<affiliation><nlm:aff wicri:cut=" and" id="AFF1">Alta Scuola Pedagogica, CH-6600 Locarno</nlm:aff>
<wicri:noCountry code="subfield">CH-6600 Locarno</wicri:noCountry>
</affiliation>
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<author><name sortKey="Egli, Martin" sort="Egli, Martin" uniqKey="Egli M" first="Martin" last="Egli">Martin Egli</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing</title>
<author><name sortKey="Pallan, Pradeep S" sort="Pallan, Pradeep S" uniqKey="Pallan P" first="Pradeep S." last="Pallan">Pradeep S. Pallan</name>
<affiliation wicri:level="1"><nlm:aff id="AFF1">Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA,</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lubini, Paolo" sort="Lubini, Paolo" uniqKey="Lubini P" first="Paolo" last="Lubini">Paolo Lubini</name>
<affiliation><nlm:aff wicri:cut=" and" id="AFF1">Alta Scuola Pedagogica, CH-6600 Locarno</nlm:aff>
<wicri:noCountry code="subfield">CH-6600 Locarno</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Bolli, Martin" sort="Bolli, Martin" uniqKey="Bolli M" first="Martin" last="Bolli">Martin Bolli</name>
<affiliation wicri:level="1"><nlm:aff id="AFF1">Actelion Pharmaceuticals Ltd., CH-4123 Allschwil, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Actelion Pharmaceuticals Ltd., CH-4123 Allschwil</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Egli, Martin" sort="Egli, Martin" uniqKey="Egli M" first="Martin" last="Egli">Martin Egli</name>
<affiliation wicri:level="1"><nlm:aff id="AFF1">Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA,</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nucleic Acids Research</title>
<idno type="ISSN">0305-1048</idno>
<idno type="eISSN">1362-4962</idno>
<imprint><date when="2007">2007</date>
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<front><div type="abstract" xml:lang="en"><p>The crystal structure of the duplex formed by oligo(2′,3′-dideoxy-<italic>β</italic>
-<sc>d</sc>
-glucopyranosyl)nucleotides (homo-DNA) revealed strongly inclined backbone and base-pair axes [Egli,M., Pallan,P.S., Pattanayek,R., Wilds,C.J., Lubini,P., Minasov,G., Dobler,M., Leumann,C.J. and Eschenmoser,A. (2006) Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system. <italic>J. Am. Chem. Soc</italic>
., 128, 10847–10856]. This inclination is easily perceived because homo-DNA exhibits only a modest helical twist. Conversely, the tight coiling of strands conceals that the backbone-base inclinations for A- (DNA and RNA) and B-form (DNA) duplexes differ considerably. We have defined a parameter <italic>η</italic>
<sub>B</sub>
that corresponds to the local inclination between sugar-phosphate backbone and base plane in nucleic acid strands. Here, we show its biological significance as a predictive measure for the relative strand polarities (antiparallel, <italic>aps</italic>
, or parallel, <italic>ps</italic>
) in duplexes of DNA, RNA and artificial nucleic acid pairing systems. The potential of formation of <italic>ps</italic>
duplexes between complementary 16-mers with eight A and U(T) residues each was investigated with DNA, RNA, 2′-<italic>O</italic>
-methylated RNA, homo-DNA and p-RNA, the ribo<italic>pyranosyl</italic>
isomer of RNA. The thermodynamic stabilities of the corresponding <italic>aps</italic>
duplexes were also measured. As shown previously, DNA is capable of forming both <italic>ps</italic>
and <italic>aps</italic>
duplexes. However, all other tested systems are unable to form stable <italic>ps</italic>
duplexes with reverse Watson–Crick (rWC) base pairs. This observation illustrates the handicap encountered by nucleic acid systems with inclinations η<sub>B</sub>
that differ significantly from 0° to form a <italic>ps</italic>
rWC paired duplex. Accordingly, RNA with a backbone-base inclination of −30<bold>°</bold>
, pairs strictly in an <italic>aps</italic>
fashion. On the other hand, the more or less perpendicular orientation of backbone and bases in DNA allows it to adopt a <italic>ps</italic>
rWC paired duplex. In addition to providing a rationalization of relative strand polarity with nucleic acids, the backbone-base inclination parameter is also a determinant of cross-pairing. Thus, systems with strongly deviating <italic>η</italic>
<sub>B</sub>
angles will not pair with each other. Nucleic acid pairing systems with significant backbone-base inclinations can also be expected to display different stabilities depending on which terminus carries unpaired nucleotides. The negative inclination of RNA is consistent with the higher stability of duplexes with 3′- compared to those with 5′-dangling ends.</p>
</div>
</front>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nucleic Acids Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Nucleic Acids Res</journal-id>
<journal-id journal-id-type="publisher-id">nar</journal-id>
<journal-id journal-id-type="hwp">nar</journal-id>
<journal-title-group><journal-title>Nucleic Acids Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">0305-1048</issn>
<issn pub-type="epub">1362-4962</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">17905816</article-id>
<article-id pub-id-type="pmc">2095819</article-id>
<article-id pub-id-type="doi">10.1093/nar/gkm612</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Structural Biology</subject>
</subj-group>
</article-categories>
<title-group><article-title>Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Pallan</surname>
<given-names>Pradeep S.</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lubini</surname>
<given-names>Paolo</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bolli</surname>
<given-names>Martin</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Egli</surname>
<given-names>Martin</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="COR1">*</xref>
</contrib>
</contrib-group>
<aff id="AFF1"><sup>1</sup>
Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA,<sup>2</sup>
Alta Scuola Pedagogica, CH-6600 Locarno and<sup>3</sup>
Actelion Pharmaceuticals Ltd., CH-4123 Allschwil, Switzerland</aff>
<author-notes><corresp id="COR1">*To whom correspondence should be addressed. <phone>+1 615 343 8070</phone>
<fax>+1 615 322 7122</fax>
<email>martin.egli@vanderbilt.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>10</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="epub"><day>28</day>
<month>9</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>28</day>
<month>9</month>
<year>2007</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
. </pmc-comment>
<volume>35</volume>
<issue>19</issue>
<fpage>6611</fpage>
<lpage>6624</lpage>
<history><date date-type="received"><day>5</day>
<month>7</month>
<year>2007</year>
</date>
<date date-type="rev-recd"><day>25</day>
<month>7</month>
<year>2007</year>
</date>
<date date-type="accepted"><day>26</day>
<month>7</month>
<year>2007</year>
</date>
</history>
<permissions><copyright-statement>© 2007 The Author(s)</copyright-statement>
<copyright-year>2007</copyright-year>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/">http://creativecommons.org/licenses/by-nc/2.0/uk/</ext-link>
) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract><p>The crystal structure of the duplex formed by oligo(2′,3′-dideoxy-<italic>β</italic>
-<sc>d</sc>
-glucopyranosyl)nucleotides (homo-DNA) revealed strongly inclined backbone and base-pair axes [Egli,M., Pallan,P.S., Pattanayek,R., Wilds,C.J., Lubini,P., Minasov,G., Dobler,M., Leumann,C.J. and Eschenmoser,A. (2006) Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system. <italic>J. Am. Chem. Soc</italic>
., 128, 10847–10856]. This inclination is easily perceived because homo-DNA exhibits only a modest helical twist. Conversely, the tight coiling of strands conceals that the backbone-base inclinations for A- (DNA and RNA) and B-form (DNA) duplexes differ considerably. We have defined a parameter <italic>η</italic>
<sub>B</sub>
that corresponds to the local inclination between sugar-phosphate backbone and base plane in nucleic acid strands. Here, we show its biological significance as a predictive measure for the relative strand polarities (antiparallel, <italic>aps</italic>
, or parallel, <italic>ps</italic>
) in duplexes of DNA, RNA and artificial nucleic acid pairing systems. The potential of formation of <italic>ps</italic>
duplexes between complementary 16-mers with eight A and U(T) residues each was investigated with DNA, RNA, 2′-<italic>O</italic>
-methylated RNA, homo-DNA and p-RNA, the ribo<italic>pyranosyl</italic>
isomer of RNA. The thermodynamic stabilities of the corresponding <italic>aps</italic>
duplexes were also measured. As shown previously, DNA is capable of forming both <italic>ps</italic>
and <italic>aps</italic>
duplexes. However, all other tested systems are unable to form stable <italic>ps</italic>
duplexes with reverse Watson–Crick (rWC) base pairs. This observation illustrates the handicap encountered by nucleic acid systems with inclinations η<sub>B</sub>
that differ significantly from 0° to form a <italic>ps</italic>
rWC paired duplex. Accordingly, RNA with a backbone-base inclination of −30<bold>°</bold>
, pairs strictly in an <italic>aps</italic>
fashion. On the other hand, the more or less perpendicular orientation of backbone and bases in DNA allows it to adopt a <italic>ps</italic>
rWC paired duplex. In addition to providing a rationalization of relative strand polarity with nucleic acids, the backbone-base inclination parameter is also a determinant of cross-pairing. Thus, systems with strongly deviating <italic>η</italic>
<sub>B</sub>
angles will not pair with each other. Nucleic acid pairing systems with significant backbone-base inclinations can also be expected to display different stabilities depending on which terminus carries unpaired nucleotides. The negative inclination of RNA is consistent with the higher stability of duplexes with 3′- compared to those with 5′-dangling ends.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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