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<StructureSection load='1y26' size='350' side='right' scene='47/479252/Cv/1' caption='Adenine riboswitch complex with adenine and Mg+2 ions, [[1y26]]'>
<StructureSection load='' size='350' side='right' scene='47/479252/Cv/1' caption='Adenine riboswitch complex with adenine and Mg+2 ions, [[1y26]]'>
__TOC__
== Function ==
== Function ==
Normally, a variety of proteins and protein cofactors control gene expression in an organism by binding to different sites on messenger RNA (mRNA). '''Riboswitches''' are genetic regulatory elements that are built directly into the RNA. They are a type of noncoding RNA that regulate gene expression in the absence of proteins by switching from one structural conformation (shape) to another in response to ligand binding.  Most contain a single binding site that recognizes a specific ligand. The ability of a riboswitch to discriminate against molecules that are similar or closely related to its ligand is essential to prevent metabolic misregulation<ref name=scimag>Breaker, Ronald R. (28 March, 2008). Complex Riboswitches. ''Science'', 319(5871), 1795-1797. doi:[http://dx.doi.org/10.1126/science.1152621 10.1126/science.1152621]</ref>.
Normally, a variety of proteins and protein cofactors control gene expression in an organism by binding to different sites on messenger RNA (mRNA). '''Riboswitches''' are genetic regulatory elements that are built directly into the [[RNA]]. They are a type of noncoding RNA that regulate gene expression in the absence of proteins by switching from one structural conformation (shape) to another in response to ligand binding.  Most contain a single binding site that recognizes a specific ligand. The ability of a riboswitch to discriminate against molecules that are similar or closely related to its ligand is essential to prevent metabolic misregulation<ref name=scimag>Breaker, Ronald R. (28 March, 2008). Complex Riboswitches. ''Science'', 319(5871), 1795-1797. doi:[http://dx.doi.org/10.1126/science.1152621 10.1126/science.1152621]</ref>.


The various classes of riboswitches discovered so far are differentiated by their respective ligands. Every class of riboswitch is characterized by an aptamer (binding site) domain, which provides the site for ligand binding, and an expression platform that undergoes conformational change. The sequences and structures of aptamer domains are highly conserved, and therefore exhibit little variation among riboswitches belonging to the same class.
The various classes of riboswitches discovered so far are differentiated by their respective '''ligands'''. Every class of riboswitch is characterized by an aptamer (binding site) domain, which provides the site for ligand binding, and an expression platform that undergoes conformational change. The sequences and structures of aptamer domains are highly conserved, and therefore exhibit little variation among riboswitches belonging to the same class.
*'''M-box riboswitch''' recognizes Mg+2<ref>PMID:21315082</ref>.
*'''YdaO riboswitch''' recognizes ATP<ref>PMID:23086297</ref>.
*'''yybp-ykoy riboswitch''' recognizes Mn+2<ref>PMID:25794618</ref>.
*'''PRPP riboswitch''' recognizes phosphoribosyl pyrophosphate<ref>PMID:29504937</ref>.
*'''ZMP riboswitch''' recognizes aminoimidazole-4-carboxamide riboside 5'-monophosphate<ref>PMID:32795418</ref>.
*'''ZTP riboswitch''' recognizes aminoimidazole-4-carboxamide riboside 5'-triphosphate<ref>PMID:32795418</ref>.
*'''ThiM riboswitch''' recognizes thiamine pyrophosphate<ref>PMID:34644399</ref>.
For details on guanine riboswitch see<br />
For details on guanine riboswitch see<br />
* [[Guanine-Binding Riboswitch]]<br />
* [[Guanine-Binding Riboswitch]]<br />
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== Structural highlights ==
== Structural highlights ==
Atomic-resolution structures of riboswitch binding sites show that they make numerous hydrogen bonds with their ligands, forming contacts that stabilize RNA interactions to further increase affinity. Some binding sites form pockets that entirely engulf the ligand, and in these instances an induced-fit mechanism of binding must occur. The riboswitch-adenine complex shows the stacking interactions of the zippered-up junctional bubble which is formed by the adenine<ref>PMID:15610857</ref>.
Atomic-resolution structures of riboswitch binding sites show that they make numerous hydrogen bonds with their ligands, forming contacts that stabilize RNA interactions to further increase affinity. Some binding sites form pockets that entirely engulf the ligand, and in these instances an induced-fit mechanism of binding must occur. The <scene name='47/479252/Cv/4'>riboswitch-adenine complex shows the stacking interactions of the zippered-up junctional bubble which is formed by the adenine</scene><ref>PMID:15610857</ref>. Water molecules are shown as red spheres.
</StructureSection>
 
==3D structures of riboswitch==
==3D structures of riboswitch==
[[Riboswitch 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*Adenine riboswitch
 
**[[1y26]], [[4tzx]], [[4tzy]], [[4xnr]] – AR + adenine – ''Vibrio vulnificus''<br />
**[[3ivn]] – BsAR (mutant) – ''Bacillus subtilis''<br />
**[[3la5]] - BsAR (mutant) + azacytosine<br />
 
*Guanine riboswitch
 
**[[1y27]] – BsGR residues 185-252 + guanine<br />
**[[2g9c]], [[3fo4]], [[3fo6]], [[3ges]], [[3gog]], [[3rkf]] - BsGR (mutant) + guanine derivative<br />
**[[3got]] - BsGR (mutant) + adenine derivative<br />
**[[2xo1]] - BsGR  aptamer domain + adenine derivative<br />
**[[3g4m]], [[3ger]] - BsGR  + guanine derivative<br />
**[[2xnz]] - BsGR  aptamer domain + guanine derivative<br />
**[[2xo0]] - BsGR  aptamer domain + triazine derivative<br />
**[[2ees]], [[2eet]], [[2eeu]], [[2eev]], [[2eew]] - BsGR (mutant) + hypoxanthine<br />
**[[3gao]] - BsGR  + xanthine<br />
**[[2xnw]] – BsGR + Mn<br />
**[[4fe5]], [[4fej]], [[4fel]], [[4fen]], [[4feo]], [[4fep]] – GR + hypoxanthine – synthetic<br />
 
*Thiamine pyrophosphate riboswitch
 
**[[2gdi]] – TPPR + TPP – synthetic<br />
**[[2hoj]], [[2hok]], [[2hol]] – EcTPPR + TPP + metal ion – ''Escherichia coli''<br />
**[[2hom]] – EcTPPR + TMP<br />
**[[2hoo]], [[2hop]] – EcTPPR + TPP analog<br />
**[[4nya]], [[4nyb]], [[4nyc]] – EcTPPR + pyrimidine derivative<br />
**[[4nyd]] – EcTPPR + hypoxanthine <br />
**[[4nyg]] – EcTPPR + thyamine <br />
**[[3d2g]], [[3d2v]], [[3d2x]] - TPPR + TPP analog – ''Arabidopsis thaliana''
 
*S-adenosylmethionine riboswitch
 
**[[2gis]], [[4aob]], [[4b5r]] – TtSAMR + SAM – ''Thermoanaerobacter tengcongensis''<br />
**[[3iqr]], [[2ydh]], [[2ygh]] - TtSAMR (mutant) + SAM<br />
**[[3iqp]] - TtSAMR<br />
**[[2qwy]], [[3e5c]], [[3e5e]], [[3e5f]], [[3iqn]] - SAMR + SAM – synthetic<br />
**[[4kqy]] – BsSAMR + SAM<br />
**[[4oqu]] - SAMR + SAM - synthetic<br />
 
*S-adenosylhomocysteine riboswitch
 
**[[3npn]], [[3npq]] – SAHR + SAH – ''Ralstonia solanacearum''<br />
 
*Lysine riboswitch
 
**[[3d0u]] – TmKR ligand-binding domain + Lysine – ''Thermotoga maritima''<br />
**[[4erj]] – TmKR + aminocaproic acid<br />
**[[4erl]] – TmKR + Lys + Gly<br />
 
*FMN riboswitch
 
**[[3f2q]], [[3f2t]], [[3f2w]], [[3f2x]], [[3f2y]], [[3f30]], [[3f4e]] – FnFMNR + FMN – ''Fusobacterium nucleatum''<br />
**[[2yie]] - FnFMNR aptamer domain + FMN<br />
**[[3f4g]], [[3f4h]] – FnFMNR + flavin derivative<br />
**[[2yif]] - FnFMNR + GTP
 
*Pre-queosine riboswitch
 
**[[3fu2]], [[3k1v]] – BsQ1R + queosine<br />
**[[3gca]] – TtQ0R + queosine<br />
**[[3q50]], [[3q51]] – TtQ1R aptamer domain + queosine<br />
**[[4jf2]] – Q1R + GTP + deaza-aminomethyl guanine – ''Lactobacillus rhamnosus''<br />
 
*C-di-GMP riboswitch
 
**[[3irw]], [[3mxh]] – VcGMPR + C-di-GMP + GTP + U1 small nuclear ribonucleoprotein – ''Vibrio cholerae''<br />
**[[3iwn]] – VcGMPR + C-di-GMP + U1 small nuclear ribonucleoprotein<br />
**[[3mum]], [[3mur]], [[3mut]] - VcGMPR (mutant) + C-di-GMP + U1 small nuclear ribonucleoprotein<br />
**[[3muv]] - VcGMPR (mutant) + C-di-AMP + U1 small nuclear ribonucleoprotein<br />
**[[3q3z]] - GMPR + C-di-GMP – ''Clostridium acetobutylicum''<br />
**[[4qk8]], [[4qka]] – GMPR + GTP – ''Thermoanaerobacter pseudethanolicus''<br />
**[[4qk9]] – GMPR + guanosine derivative – ''Thermovirga lienii''<br />
 
*Glycine riboswitch
 
**[[3owi]], [[3oww]], [[3owz]] – VcGlyR + glycine<br />
**[[3ox0]], [[3oxe]], [[3oxj]], [[3oxm]] – VcGlyR + GDP + cytidine cyclic phosphate<br />
**[[3oxb]], [[3oxd]] – VcGlyR (mutant) + GDP + cytidine cyclic phosphate<br />
**[[3p49]] – FnGlyR + U1 small nuclear ribonucleoprotein + glycine<br />
 
*M-Box riboswitch
 
**[[3pdr]] – BsMBR + Mn<br />
 
*T-Box riboswitch
 
**[[4lck]] – sTBR + tRNA-Gly + ribosomal protein YBXF – synthetic<br />
**[[4mgn]] – sTBR + tRNA-Gly <br />
 
*Tetrahydrofolate riboswitch
 
**[[3suh]], [[3sux]] – EsTHFR + THF derivative – ''Eubacterium siraeum''<br />
**[[3suy]] - EsTHFR + cytidine cyclic phosphate<br />
**[[3sd1]], [[4lvv]], [[4lvx]], [[4lvw]], [[4lvy]], [[4lvz]], [[4lw0]] – THFR + purine derivative – synthetic<br />
**[[3sd3]] – THFR (mutant) + pteridine derivative – synthetic<br />
 
*Fluoride riboswitch
 
**[[3vrs]] – TpR + Mn + K + F – ''Thermotoga petrophila''<br />
**[[4en5]] – TpR + Mg + Tl + F <br />
**[[4enc]] – TpR + Mg + K + F <br />
**[[4ena]] – TpR + Mg + Cs + GTP + F <br />
**[[4enb]] – TpR + Mg + Ir + K + GTP + F <br />
 
*Cobalamine riboswitch
 
**[[4frg]], [[4frn]], [[4gma]], [[4gxy]] – CoR + aptamer domain – ''Marine metagenome''<br />
 
*yybp-ykoy riboswitch
 
**[[4y1i]] – LlYYR + Mn – ''Lactobacillus lactis''<br />
**[[4y1j]] – LlYYR (mutant) + Mn<br />
**[[4y1m]] – EcYYR <br />


}}
== References ==
== References ==
<references/>
<references/>
[[Category: Topic Page]]
[[Category: Topic Page]]

Latest revision as of 11:43, 11 August 2024

Function

Normally, a variety of proteins and protein cofactors control gene expression in an organism by binding to different sites on messenger RNA (mRNA). Riboswitches are genetic regulatory elements that are built directly into the RNA. They are a type of noncoding RNA that regulate gene expression in the absence of proteins by switching from one structural conformation (shape) to another in response to ligand binding. Most contain a single binding site that recognizes a specific ligand. The ability of a riboswitch to discriminate against molecules that are similar or closely related to its ligand is essential to prevent metabolic misregulation[1].

The various classes of riboswitches discovered so far are differentiated by their respective ligands. Every class of riboswitch is characterized by an aptamer (binding site) domain, which provides the site for ligand binding, and an expression platform that undergoes conformational change. The sequences and structures of aptamer domains are highly conserved, and therefore exhibit little variation among riboswitches belonging to the same class.

  • M-box riboswitch recognizes Mg+2[2].
  • YdaO riboswitch recognizes ATP[3].
  • yybp-ykoy riboswitch recognizes Mn+2[4].
  • PRPP riboswitch recognizes phosphoribosyl pyrophosphate[5].
  • ZMP riboswitch recognizes aminoimidazole-4-carboxamide riboside 5'-monophosphate[6].
  • ZTP riboswitch recognizes aminoimidazole-4-carboxamide riboside 5'-triphosphate[7].
  • ThiM riboswitch recognizes thiamine pyrophosphate[8].

For details on guanine riboswitch see

Structural highlights

Atomic-resolution structures of riboswitch binding sites show that they make numerous hydrogen bonds with their ligands, forming contacts that stabilize RNA interactions to further increase affinity. Some binding sites form pockets that entirely engulf the ligand, and in these instances an induced-fit mechanism of binding must occur. The [9]. Water molecules are shown as red spheres.

3D structures of riboswitch

Riboswitch 3D structures


Adenine riboswitch complex with adenine and Mg+2 ions, 1y26

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Breaker, Ronald R. (28 March, 2008). Complex Riboswitches. Science, 319(5871), 1795-1797. doi:10.1126/science.1152621
  2. ↑ Ramesh A, Wakeman CA, Winkler WC. Insights into Metalloregulation by M-box Riboswitch RNAs via Structural Analysis of Manganese-Bound Complexes. J Mol Biol. 2011 Apr 8;407(4):556-70. Epub 2011 Feb 15. PMID:21315082 doi:10.1016/j.jmb.2011.01.049
  3. ↑ Watson PY, Fedor MJ. The ydaO motif is an ATP-sensing riboswitch in Bacillus subtilis. Nat Chem Biol. 2012 Dec;8(12):963-5. PMID:23086297 doi:10.1038/nchembio.1095
  4. ↑ Dambach M, Sandoval M, Updegrove TB, Anantharaman V, Aravind L, Waters LS, Storz G. The ubiquitous yybP-ykoY riboswitch is a manganese-responsive regulatory element. Mol Cell. 2015 Mar 19;57(6):1099-1109. PMID:25794618 doi:10.1016/j.molcel.2015.01.035
  5. ↑ Sherlock ME, Sudarsan N, Stav S, Breaker RR. Tandem riboswitches form a natural Boolean logic gate to control purine metabolism in bacteria. Elife. 2018 Mar 5;7:e33908. PMID:29504937 doi:10.7554/eLife.33908
  6. ↑ Tran B, Pichling P, Tenney L, Connelly CM, Moon MH, Ferré-D'Amaré AR, Schneekloth JS Jr, Jones CP. Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design. Cell Chem Biol. 2020 Oct 15;27(10):1241-1249.e4. PMID:32795418 doi:10.1016/j.chembiol.2020.07.021
  7. ↑ Tran B, Pichling P, Tenney L, Connelly CM, Moon MH, Ferré-D'Amaré AR, Schneekloth JS Jr, Jones CP. Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design. Cell Chem Biol. 2020 Oct 15;27(10):1241-1249.e4. PMID:32795418 doi:10.1016/j.chembiol.2020.07.021
  8. ↑ Du C, Wang Y, Gong S. Regulation of the ThiM riboswitch is facilitated by the trapped structure formed during transcription of the wild-type sequence. FEBS Lett. 2021 Nov;595(22):2816-2828. PMID:34644399 doi:10.1002/1873-3468.14202
  9. ↑ Serganov A, Yuan YR, Pikovskaya O, Polonskaia A, Malinina L, Phan AT, Hobartner C, Micura R, Breaker RR, Patel DJ. Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs. Chem Biol. 2004 Dec;11(12):1729-41. PMID:15610857 doi:S1074-5521(04)00343-6

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