2'-dG

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Rfam ID: RF00167 (Purine riboswitch)

    RF03165 (2dG-II purine riboswitch)


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Timeline Description Structure&recognition References


Timeline

Start

    2007[2] Discovery of 2'-dG-I riboswitch

    Crystal structure of 2'-dG-I riboswitch bound to 2'-dG 2011[3]

    2017[4] Discovery of 2'-dG-II riboswitch

    Crystal structure of 2'-dG-II riboswitch bound to 2'-dG 2019[5]

    2022[6] Discovery of 2'-dG-III riboswitch
2023...



Description

 Carrying an aptamer domain similar in sequence and secondary structure to the guanine riboswitch, the 2'-dG riboswitch exhibits improved affinities for 2'-deoxyguanosine (2'-dG), 3'-deoxyguanosine (3'-dG) and guanosine, and contains a uracil ribonucleotide in a conserved position of the ligand-binding aptamer domain. Up to now, three classes of 2'-dG riboswitches, named 2'-dG-I, 2'-dG-II and 2'-dG-III, have been identified, wherein the first two classes of 2'-dG riboswitches have atomic-resolution structural models[2-6].


Gene association

The gene associateds with 2'-dG-I, 2'-dG-II and 2'-dG-III RNAs are different from each other. 2'-dG-I RNAs in Mesoplasma florum are associated with genes annotated as ribonucleotide reductase. Genes located downstream from 2'-dG-II RNAs in Gracillimonas tropica are predicted to encode a signal receiver domain, endonuclease I, phospholipase D, and ComEC. ComEC is a competence protein involved in importing foreign DNA and endonuclease I could mitigate a lack of 2'-dG by salvaging deoxyribonuc. 2'-dG-III RNAs from Bacillus sp. are associated with genes encoding for purine nucleoside hydrolase, which uses nucleosides as substrates and produces free nucleobases as products[2,4,6].
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Gene regulation

Putative mechanisms for regulation of gene expression by 2'-dG-I in in Mesoplasma florum, 2'-dG-II in Gracillimonas tropica and 2'-dG-III in Bacillus sp. are shown below. We present the prototypical mechanism, but not all possible mechanisms[2,4,6].
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Structure and Ligand recognition

2D representation

Top: Consensus sequence and secondary structure model for riboswitches that recognize purines, which are dominated by guanine riboswitches. Bottom: Secondary structure depictions of the 2'-dG-II riboswitch in an environmental sequence sample according to PDB ID: 6P2H[1,4,6].

5'GGGUGUAAUCUCCAAAAUAUGGUUGGGGAGCCUCCACCAGUGAACCGUAAAAUCGCUGUCACCACCCAG3' (Sequence from bottom structure )


3D visualisation

The overall structure of the 2'-dG-I riboswitch in Mesoplasma florum was generated from PDB ID: 3SKI at 2.30 Å resolution bound with 2'-dG. 2'-dG (shown in sticks) is labeled in red. Additional available structures that have been solved and detailed information are accessible on Structures page [3].

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drawing PDBe Molstar






The overall structure of the 2'-dG-II riboswitch in an environmental sequence sample was generated from PDB ID: 6P2H at 2.80 Å resolution bound with 2'-dG. 2'-dG (shown in sticks) is labeled in red. Additional available structures that have been solved and detailed information are accessible on Structures page [5].

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Binding pocket

Left: Surface representation of the binding pocket of the 2'-dG-I riboswitch in Mesoplasma florum generated from PDB ID: 3SKI at 2.30 Å. 2'-dG (shown in sticks) is labeled in red. Right: The hydrogen bonds of the binding sites of the 2'-dG-I riboswitch bound with 2'-dG[3].
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Left: Surface representation of the binding pocket of the 2'-dG-II riboswitch in an environmental sequence sample generated from PDB ID: 6P2H 2.80 Å. 2'-dG (shown in sticks) is labeled in red. Right: The hydrogen bonds of the binding sites of the 2'-dG-II riboswitch bound with 2'-dG[5].
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Ligand recognition

Chemical structures of 2'-deoxyguanosine (2'-dG) and its analogs. The apparent KD of each compound of three classes of 2'-dG riboswitches is shown on bottom. Refer to the corresponding references for comprehensive details regarding reaction conditions and species information in measuring the dissociation constant displayed below[2,4,6].
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References

[1] Interactions between deoxyribonucleotide and DNA synthesis.
Reichard, P.
Annu. Rev. Biochem. 57, (1988).

[2] Guanine riboswitch variants from Mesoplasma florum selectively recognize 2'-deoxyguanosine.
Kim, J. N., Roth, A. & Breaker, R. R.
Proc. Natl. Acad. Sci. U. S. A. 104, (2007).

[3] Structural principles of nucleoside selectivity in a 2'-deoxyguanosine riboswitch.
Pikovskaya, O., Polonskaia, A., Patel, D. J. & Serganov, A.
Nat. Chem. Biol. 7, (2011).

[4] Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity.
Weinberg, Z., Nelson, J. W., Lünse, C. E., Sherlock, M. E. & Breaker, R. R.
Proc. Natl. Acad. Sci. U. S. A. 114, (2017).

[5] Structural basis for 2'-deoxyguanosine recognition by the 2'-dG-II class of riboswitches.
Matyjasik, M. M. & Batey, R. T.
Nucleic Acids Res. 47, (2019).

[6] Variants of the guanine riboswitch class exhibit altered ligand specificities for xanthine, guanine, or 2'-deoxyguanosine.
Hamal, D. S., Panchapakesan, S. S. S., Slattery, P., Roth, A. & Breaker, R. R.
Proc. Natl. Acad. Sci. U. S. A. 119, (2022).