Z-DNA: Difference between revisions
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Z-DNA (<scene name='Sandbox_Z-DNA/B-z/7'>B-Z DNA junction</scene>, PDB entry [[2acj]]) can form ''invitro'' from B-DNA by raising negative super helical stress or under low salt conditions when deoxycytosine is 5-methylated. The formation of Z-DNA ''invivo'' is an energy requiring process. It forms behind a RNA polymerase moving through a DNA double helix during transcription and is subsequently stabilized due to the generation of negative supercoils. Z-DNA is the first single crystal X-ray structure of a DNA fragment. It was crystallized as a self complementary DNA hexamer d(CG)<sub>3</sub> by Andrew Wang, Alexander Rich and their co-workers at MIT in 1979. <ref name = 'Rich'>PMID:12838348</ref><ref name ='Wang'>PMID:17485386</ref> | Z-DNA (<scene name='Sandbox_Z-DNA/B-z/7'>B-Z DNA junction</scene>, PDB entry [[2acj]]) can form ''invitro'' from B-DNA by raising negative super helical stress or under low salt conditions when deoxycytosine is 5-methylated. The formation of Z-DNA ''invivo'' is an energy requiring process. It forms behind a RNA polymerase moving through a DNA double helix during transcription and is subsequently stabilized due to the generation of negative supercoils. Z-DNA is the first single crystal X-ray structure of a DNA fragment. It was crystallized as a self complementary DNA hexamer d(CG)<sub>3</sub> by Andrew Wang, Alexander Rich and their co-workers at MIT in 1979. <ref name = 'Rich'>PMID:12838348</ref><ref name ='Wang'>PMID:17485386</ref> | ||
Whenever B-DNA transforms into Z-DNA two<scene name='Sandbox_Z-DNA/B-zjunction/7'> B-Z junctions </scene> form. The crystal structure of these junctions revealed<scene name='Sandbox_Z-DNA/Extruded/12'> two extruded bases</scene>, <scene name='Z-DNA/Extruded/2'>adenine</scene> and <scene name='Z-DNA/Extruded/3'>thymine</scene> at the junction. A crucial finding from this structure is that a right handed DNA can transform to a left handed DNA or vice versa by the disruption and extrusion of a base pair. It has also been suggested that the extruded base pairs at B-Z DNA junction may be sites for DNA modification.<ref>PMID:16237447</ref> | Whenever B-DNA transforms into Z-DNA two <scene name='Sandbox_Z-DNA/B-zjunction/7'>B-Z junctions</scene> form. The crystal structure of these junctions revealed<scene name='Sandbox_Z-DNA/Extruded/12'> two extruded bases</scene>, <scene name='Z-DNA/Extruded/2'>adenine</scene> and <scene name='Z-DNA/Extruded/3'>thymine</scene> at the junction. A crucial finding from this structure is that a right handed DNA can transform to a left handed DNA or vice versa by the disruption and extrusion of a base pair. It has also been suggested that the extruded base pairs at B-Z DNA junction may be sites for DNA modification.<ref>PMID:16237447</ref> | ||
== Z-DNA binding proteins == | == Z-DNA binding proteins == | ||
=== Double Stranded RNA adenosine deaminase 1, ADAR1 === | === Double Stranded RNA adenosine deaminase 1, ADAR1 === | ||
ADAR1 <scene name='Sandbox_Z-DNA/Adar1/3'> | ADAR1 (<scene name='Sandbox_Z-DNA/Adar1/3'>Z-ALPHA and Z-DNA complex</scene>, [[1qbj]]) belongs to the family of deaminases that modify double stranded mRNA by catalyzing the conversion of adenine to inosine which is then translated to guanosine. It is a complex protein with two Z-DNA binding motifs called <scene name='Sandbox_Z-DNA/Adar1zalpha/10'>Z-alpha</scene> and Z-beta.<ref name = 'Wang'>PMID:17485386</ref> ADAR1 also has three copies of double-stranded RNA binding motif (DRBM) and a catalytic domain related to ''E.coli'' cytidine deaminase. The binding motif Z-alpha belongs to winged-helix-turn-helix family of proteins. It consists of a <scene name='Z-DNA/Adar1zalpha/1'>helix-turn-helix motif</scene> which has two alpha helices (<scene name='Z-DNA/Adar1zalpha/2'>alpha-2</scene> and <scene name='Z-DNA/Adar1zalpha/3'>alpha-3 also called the recognition</scene>) connected by a short strand of amino acids and a <scene name='Sandbox_Z-DNA/Adar1zalpha/15'>C- terminal beta-sheet</scene>. The beta sheet constrains the fold by contacting the residues between alpha-2 and alpha-3. | ||
The contact surface between <scene name='Sandbox_Z-DNA/Adar1/4'>Z-alpha and DNA</scene> consists of residues from the helix alpha-3 and COOH-terminal beta hairpin. Hydrogen bonding is present between <scene name='Z-DNA/Aminoacid/1'>amino acids</scene> Lys<sup>169</sup>, Lys <sup>170</sup>, Asn<sup>173</sup>, Arg<sup>174</sup> and Tyr<sup>177</sup> in the helix alpha-3 and <scene name='Z-DNA/Dnanucleotides/2'>five consecutive phosphates on Z-DNA</scene>. Lys<sup>169</sup>, Asn<sup>173</sup>, Arg<sup>174</sup>, Trp<sup>195</sup> make water mediated phosphate contacts with Z-DNA. In addition Thr<sup>191</sup> and Arg<sup>174</sup> <scene name='Z-DNA/Thrarg/1'>bind to the furanose oxygens</scene> of G2 and G6 on Z-DNA. An important interaction is the <scene name='Z-DNA/Tyrosine_and_g4/1'>Vanderwaal's bond</scene> between aromatic ring of Tyr<sup>177</sup> and the carbon 8 of G4. This is unique to Z-DNA as the interaction requires the base to be in syn conformation. Pro<sup>192</sup>, Pro <sup>193</sup> form another set of <scene name='Z-DNA/Pro/1'>important Vanderwaal's interactions</scene> with Z-DNA where the pyrrolidine rings bond with the sugar-phosphate backbone from phosphate 2 to phosphate 3. Pro<sup>192</sup> is conserved in Z-alpha and its homologues and forms a cis peptide bond which positions beta loop against the Z-DNA surface.<ref name = SchwartzRich>PMID: 10364558</ref> | The contact surface between <scene name='Sandbox_Z-DNA/Adar1/4'>Z-alpha and DNA</scene> consists of residues from the helix alpha-3 and COOH-terminal beta hairpin. Hydrogen bonding is present between <scene name='Z-DNA/Aminoacid/1'>amino acids</scene> Lys<sup>169</sup>, Lys <sup>170</sup>, Asn<sup>173</sup>, Arg<sup>174</sup> and Tyr<sup>177</sup> in the helix alpha-3 and <scene name='Z-DNA/Dnanucleotides/2'>five consecutive phosphates on Z-DNA</scene>. Lys<sup>169</sup>, Asn<sup>173</sup>, Arg<sup>174</sup>, Trp<sup>195</sup> make water mediated phosphate contacts with Z-DNA. In addition Thr<sup>191</sup> and Arg<sup>174</sup> <scene name='Z-DNA/Thrarg/1'>bind to the furanose oxygens</scene> of G2 and G6 on Z-DNA. An important interaction is the <scene name='Z-DNA/Tyrosine_and_g4/1'>Vanderwaal's bond</scene> between aromatic ring of Tyr<sup>177</sup> and the carbon 8 of G4. This is unique to Z-DNA as the interaction requires the base to be in syn conformation. Pro<sup>192</sup>, Pro <sup>193</sup> form another set of <scene name='Z-DNA/Pro/1'>important Vanderwaal's interactions</scene> with Z-DNA where the pyrrolidine rings bond with the sugar-phosphate backbone from phosphate 2 to phosphate 3. Pro<sup>192</sup> is conserved in Z-alpha and its homologues and forms a cis peptide bond which positions beta loop against the Z-DNA surface.<ref name = SchwartzRich>PMID: 10364558</ref> | ||
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Z-DNA binding proteins have common structural characteristics. The binding domains of these proteins can substitute one another and thus can act as competitive inhibitors against one another. As explained above, disruption in the Z-DNA binding region of E3L reduces its pathogenicity. All these observations are important pointers towards the biological importance of Z-DNA.<ref name ='Wang'>PMID:17485386</ref> | Z-DNA binding proteins have common structural characteristics. The binding domains of these proteins can substitute one another and thus can act as competitive inhibitors against one another. As explained above, disruption in the Z-DNA binding region of E3L reduces its pathogenicity. All these observations are important pointers towards the biological importance of Z-DNA.<ref name ='Wang'>PMID:17485386</ref> | ||
</StructureSection> | |||
== Movie Depicting ADAR1 binding to Z-DNA == | == Movie Depicting ADAR1 binding to Z-DNA == | ||
<qt>file=Movie3_Z-DNA.mov|width=320|height=280|autoplay=false|controller=true</qt> | <qt>file=Movie3_Z-DNA.mov|width=320|height=280|autoplay=false|controller=true</qt> | ||
