Hoogsteen base pair: Difference between revisions

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{{Short description|Nucleic acid pairing variations}}

[[File:Hoogsteen Watson Crick pairing-en.svg|thumb|400px|Chemical structures for Watson-CrickWatson–Crick and Hoogsteen A•T and G•C+ base pairs. The Hoogsteen geometry can be achieved by purine rotation around the glycosidic bond (χ) and base-flipping (θ), affecting simultaneously C8 and C1′C1{{prime}} (yellow).<ref name="Nikolova">{{cite journal |title=Transient Hoogsteen base pairs in canonical duplex DNA|author1=Evgenia N. Nikolova |author2=Eunae Kim |author3=Abigail A. Wise |author4=Patrick J. O'Brien |author5=Ioan Andricioaei |author6=Hashim M. Al-Hashimi |journal=Nature|year=2011|volume=470|issue=7335|pages=498–502|doi=10.1038/nature09775|pmid=21270796 |bibcode=2011Natur.470..498N|pmc=3074620}}</ref>]]

A '''Hoogsteen base pair''' is a variation of base-pairing in [[nucleic acid]]s such as the A•T pair. In this manner, two [[nucleobase]]s, one on each strand, can be held together by [[hydrogen bond]]s in the major groove. ASpecifically, Hoogsteenit [[basehappens pair]]when applies the N7 position of thea [[purinepyrimidine]] base (as a [[hydrogen bond]] acceptorC/T) and C6uses aminoits groupWatson–Crick (as''anti'', a donorN³&ndash;C⁴), whichface to bind the Watson-Crick''syn'' (N3N⁶&ndash;C4N⁷) face of thea [[pyrimidinepurine]] base(A/G).

[[Adenine]], which is not a pyrimidine, is capable of using its ''anti'' (N¹&ndash;N⁶) face to pair with the ''syn'' face of a purine to form a Hoogsteen-like base pair.<ref>{{cite journal |last1=Pan |first1=B |last2=Mitra |first2=SN |last3=Sundaralingam |first3=M |title=Crystal structure of an RNA 16-mer duplex R(GCAGAGUUAAAUCUGC)2 with nonadjacent G(syn).A+(anti) mispairs. |journal=Biochemistry |date=2 March 1999 |volume=38 |issue=9 |pages=2826-31 |doi=10.1021/bi982122y |pmid=10052954}}</ref> [[Guanine]] can form a similar interaction with another purine base, forming a rigid cycle called a [[guanine tetrad]] in the case of four guanines. These are also "Hoogsteen base pairs" under the expanded understanding as ''anti''-''syn'' interaction.<ref name="Smith"/>

[[File:Nucleobase_edges.png|alt=|thumb|Base pairing edge of nucleobases under the general view. Top figure is an example of a purine (Adenine) where the edges are known as Watson-Crick (''anti''), Hoogsteen (''syn''), and Sugar Edges. Bottom figure is an example of a Pyrimidine (Cytosine) with the Watson-Crick (''anti''), C-H (''syn''), and Sugar Edges.]]

A '''reverse Hoogsteen base pair''' is when a pyrimidine's ''syn'' (N³&ndash;C²) face binds a purine's ''syn'' face.<ref>{{cite web |title=Hoogsteen and reverse Hoogsteen base pairs |website=X3DNA-DSSR: a resource for structural bioinformatics of nucleic acids|url=https://x3dna.org/highlights/hoogsteen-and-reverse-hoogsteen-base-pairs }}</ref> Under a systemic view of [[non-canonical base pairing]], Hoogsteen base pairs (in the expanded sense) are called Watson-Crick/Hoogsteen, based on what faces are interacting (the ''syn'' face is called the Hoogsteen face). The reverse Hoogsteen base pair is called "Hoogsteen/Hoogsteen".<ref name="Halder_2013">{{cite journal | vauthors = Halder S, Bhattacharyya D | title = RNA structure and dynamics: a base pairing perspective | journal = Progress in Biophysics and Molecular Biology | volume = 113 | issue = 2 | pages = 264–83 | date = November 2013 | pmid = 23891726 | doi = 10.1016/j.pbiomolbio.2013.07.003 }}</ref>

==Notation==

This article employs the "•" character in describing any noncovalant interaction, which can include Hoogsteen, reverse Hoogsteen, and Watson-Crick base pairs, in line with IUPAC's 1970 recommendation.<ref name=iupac70>{{Cite journal | author = IUPAC-IUB Commission on Biochemical Nomenclature | doi = 10.1021/bi00822a023 | title = Abbreviations and symbols for nucleic acids, polynucleotides, and their constituents | journal = [[Biochemistry (journal)|Biochemistry]] | volume = 9 | issue = 20 | pages = 4022–4027 | year = 1970|url=https://iupac.qmul.ac.uk/misc/naabb.html }}</ref>{{rp|at=N3.4.2}}

According to the IUPAC, "-" is not acceptable because it implies covalent linkage and neither are ":" and "/" because they can be mistaken as ratios. Not using any symbol is also unacceptable because it can be confused with a (covalent) polymer sequence.<ref name=iupac70/>{{rp|at=N3.4.2}}

IUPAC makes no specific recommendation for differentiating types of noncovalant bonds. When it is necessary to differentiate, this article uses "*" for the Hogsteen pair, "□" for the Watson-Crick pair, and "△" for the reverse Hoogsteen pair.<!-- Not to be confused with △○✕□. --> The typical Hogsteen pairs are A*T and G*C⁺ (note the charge on [[cytidine]], indicating [[protonation]]).

==History==

Ten years after [[James Watson]] and [[Francis Crick]] published their model of the DNA double helix,<ref name="Watson">{{cite journal |title=Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid|vauthors=Watson JD, Crick FH |journal=Nature|year=1953|volume=171|issue=4356|pages=737–738|doi=10.1038/171737a0|pmid=13054692|bibcode=1953Natur.171..737W|s2cid=4253007 }}</ref> [[Karst Hoogsteen]] reported<ref>{{cite journal |title=The crystal and molecular structure of a hydrogen-bonded complex between 1-methylthymine and 9-methyladenine|authorvauthors = Hoogsteen K|journal=Acta Crystallographica|year=1963|volume=16|issue=9|pages=907–916|doi=10.1107/S0365110X63002437|doi-access=free}}</ref> a crystal structure of a complex in which analogues of A and T formed a base pair that had a different geometry from that described by Watson and Crick. Similarly, an alternative base-pairing geometry can occur for G•C pairs. Hoogsteen pointed out that if the alternative hydrogen-bonding patterns were present in DNA, then the double helix would have to assume a quite different shape. Hoogsteen base pairs are observed in alternative structures such as the four-stranded [[G-quadruplex]] structures that form in DNA and RNA.

==Chemical properties==

Hoogsteen pairs have quite different properties from [[base pair|Watson-CrickWatson–Crick base pairs]]. The angle between the two glycosidic bonds (ca. 80° in the A• A*T pair) is larger and the C1&{{prime;}}&ndash;C1&{{prime;}} distance (ca. 860 pm or 8.6 Å) is smaller than in the regular geometry. In some cases, called ''reversed Hoogsteen base pair''s, one base is rotated 180° with respect to the other.

In some DNA sequences, especially CA and TA dinucleotides, Hoogsteen base pairs exist as transient entities that are present in thermal equilibrium with standard Watson–Crick base pairs. The detection of the transient species required the use of NMR techniquesrelaxation thatdispersion have only recently beenspectroscopy applied to macromolecules.<ref name="Nikolova"/>

Hoogsteen base pairs have been observed in protein–DNA complexes.<ref name="Aishima">{{cite journal |title=A Hoogsteenvauthors base= pairAishima embeddedJ, inGitti undistortedRK, B‐DNA|author=JunNoah AishimaJE, RossitzaGan K.HH, GittiSchlick T, JoyceWolberger E.C Noah,| Hintitle Hark= Gan,A [[TamarHoogsteen Schlick]],base Cynthiapair embedded in undistorted B-DNA Wolberger| journal = Nucleic Acids Res |year=2002| volume = 30 | issue = 23 | pages =5244–5252 5244–52 |doi date =10.1093/nar/gkf661 December 2002 | pmid = 12466549 | pmc = 137974 | doi = 10.1093/nar/gkf661 }}</ref> Some proteins have evolved to recognize only one base-pair type, and use intermolecular interactions to shift the equilibrium between the two geometries.

DNA has many features that allow its sequence-specific recognition by proteins. This recognition was originally thought to primarily involve specific hydrogen-bonding interactions between amino-acid side chains and bases. But it soon became clear that there was no identifiable one-to-one correspondence — that is, there was no simple code to be read. Part of the problem is that DNA can undergo conformational changes that distort the classical double helix. The resulting variations alter the presentation of DNA bases to proteins molecules and thus affect the recognition mechanism.

As distortions in the double helix are themselves are dependent on base sequence, proteins are able to recognize DNA in a manner similar to the way that they recognize other proteins and small ligand molecules, i.e. via geometric shape (instead of the specific sequence). For example, stretches of A and T bases can lead to narrowing the minor groove of DNA (the narrower of the two grooves in the double helix), resulting in enhanced local negative electrostatic potentials which in turn creates binding sites for positively charged [[arginine]] amino-acid residues on the protein.

==Triplex structures==

[[File:Hoogsteen.png|thumb|right|200px|Base triads in a DNA triple helix structure. Includes four standard Hogsteen examples and two nonstandard adenine examples.]]

This non-Watson-CrickWatson–Crick base-pairing allows the third strands to wind around the duplexes, which are assembled in the [[base pair|Watson-CrickWatson–Crick pattern]], and form [[triple-stranded DNA|triple-stranded helices]] such as (poly(dA)•2poly(dT) = poly(dT)*poly(dA)□poly(dT)) and (poly(rG)•2poly(rC) = poly(rC)*poly(rG)□poly(rC)).<ref name="pmid7578246">{{cite journal |last1 vauthors = Kim |first1=SK, |last2=Takahashi |first2=M, |last3=Nordén |first3=B | title = Binding of RecA to anti-parallel poly(dA).2poly(dT) triple helix DNA. | journal =Biochimica etBiochim BiophysicaBiophys Acta |date=17 October 1995 |volume=1264 |issue=1 |pages=129–331264 |pmid=7578246|doi=10.1016/0167-4781(95)00137-6 }}</ref>issue It can be also seen in three-dimensional structures of [[transfer RNA]], as T54•A58 and U8•A14.<ref name="pmid12853610">{{cite journal1 |last1=Zagryadskaya |first1=EIpages |last2=Doyon |first2=FR129–33 |last3=Steinberg |first3=SVdate |title=Importance ofOctober the reverse Hoogsteen base pair 54-58 for tRNA function.1995 |journal=Nucleic Acidspmid Research |date=15 July 20037578246 |volume=31 |issue=14doi |pages=3946–53 |pmid=12853610 |pmc=165963|doi=10.10931016/nar/gkg448 }}</ref><ref>{{cite book |last1=Westhof |first1=Eric |last2=Auffinger |first2=Pascal |title=Encyclopedia of life sciences. |publisher=Nature Pub. Group |isbn=9780470015902 |chapter0167-url=http://www4781(95)00137-ibmc.u-strasbg.fr/upr9002/westhof/PDF/r2001_EWesthof_ELS.pdf |access-date=28 March 2019 |chapter=Transfer RNA Structure|date=2005-09-096 }}</ref>

The reverse Hogsteen pair can be seen in three-dimensional structures of [[transfer RNA]], as T54△A58 and U8△A14.<ref name="pmid12853610">{{cite journal | vauthors = Zagryadskaya EI, Doyon FR, Steinberg SV | title = Importance of the reverse Hoogsteen base pair 54-58 for tRNA function | journal = Nucleic Acids Res | volume = 31 | issue = 14 | pages = 3946–53 | date = July 2003 | pmid = 12853610 | pmc = 165963 | doi = 10.1093/nar/gkg448 }}</ref><ref>{{cite book |vauthors = Westhof E, Auffinger P |title=Encyclopedia of life sciences. |publisher=Nature Pub. Group |isbn=9780470015902 |chapter-url=http://www-ibmc.u-strasbg.fr/upr9002/westhof/PDF/r2001_EWesthof_ELS.pdf |access-date=28 March 2019 |chapter=Transfer RNA Structure|date=2005-09-09 }}</ref>

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==Quadruplex structures==

[[File:G-quadruplex.svg|Left: A guanine tetrad featuring a central cation <br /> Right: Three guanine tetrads contributing to the structure of a G-quadruplex|thumb|330px]]

HoogsteenAs pairsmentioned alsobefore, four guanine bases can form a rigid cycle called a [[guanine tetrad]]. This allows formation of secondary structures of G-rich single stranded DNA and RNA G-rich called [[G-quadruplex]]es (G4-DNA and G4-RNA). Evidence exists for both in vitro and in vivo formation of G4s. Genomic G4s have been suggested to regulate gene transcription and at the RNA level inhibit protein synthesis through steric inhibition of ribosome function. It needs four triplets of G, separated by short spacers. This permits assembly of planar quartets which are composed of stacked associations of Hoogsteen bonded guanine molecules.<ref name="Smith">{{cite journal | vauthors = Johnson JE, Smith JS, Kozak ML, Johnson FB | title ='' In vivo veritas'': Usingusing yeast to probe the biological functions of G-quadruplexes |vauthors journal =Johnson JE,Biochimie Smith| JS,volume Kozak= ML,90 Johnson| FBissue = 8 |journal pages =Biochimie 1250–63 |year date = August 2008 |volume pmid =90 18331848 |issue pmc =8|pages=1250–1263 2585026 | doi = 10.1016/j.biochi.2008.02.013|pmid=18331848|pmc=2585026 }}</ref>

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==Triple-helix base pairing==

Watson-Crick base pairs are indicated by a "•", "-", or a "." (example: A•T, or poly(rC)•2poly(rC)).

Hoogsteen [[triple-stranded DNA]] base pairs are indicated by a "*" or a ":" (example: C•G*C+, T•A*T, C•G*G, or T•A*A).

==See also==

* [[Wobble base pair]]

* [[G-quadruplex]]

* [[Guanine tetrad]]

* [[Nucleic acid tertiary structure]]

* [[Polypurine reverse-Hoogsteen hairpin]]s (PPRHs), oligonucleotides that can bind either DNA or RNA and decrease gene expression.