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| {{Sandbox_Reserved_JMeans}} | | {{Sandbox_Reserved_JMeans}} |
| <!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | | <!-- PLEASE ADD YOUR CONTENT BELOW HERE --> |
| <Structure load='3RJ1' size='400' frame='true' align='left' caption='Mediator' scene='Insert optional scene name here' /> | | |
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| | <Structure load='3RJ1' size='400' frame='true' align='right' caption='Mediator' scene='Insert optional scene name here' /> |
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| == Mediator == | | == Mediator == |
| ''' | | The mediator, found in the yeast ''S. cerevisiae'', connects repressors and activators bound to regulatory DNA with RNA polymerase II (Pol II). As a result, the mediator is an important regulator of eukaryotic transcription.<ref>PMID: 21725323 </ref> Also, mediator is currently being studied because of its ability and role to regulate gene expression.<ref>PMID: 20299225 </ref> Mediator is in the form of three main modules, which are the tail, arm, and head. The <scene name='Sandbox_Reserved_387/Head_module/1'>head module</scene> of the mediator is split into three domains that go through significant conformational changes, and it interacts with the Rpb7 and Rpb4 subunits of Pol II and TATA binding protein subunit of transcription factor TFIID.<ref name="nature">PMID: 21725323 </ref> |
| Riboswitches are highly conserved metabolite binding domains that are present in the 5'-untranslated region (5'-UTR) of certain mRNAs in bacteria which can act in the absence of protein cofactors. Riboswitches have been found to be broadly distributed among all forms of life, but all most frequently found in bacteria. These structural elements bind specific metabolites in the aptamer (binding site) domain that results in allosteric rearrangement in the adjacent expression platform that interacts with RNA elements to regulate gene expression associated with biosythesis and transport. In bacteria, riboswitches account for the regulation of 2% of the genes, thus making them attractive for genetic research.
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| Within the bacterium, ''Bacillus subtilus'', the guanine riboswitch is found. The <scene name='Sandbox_Reserved_402/Initial_structure_with_bases/2'>guanine riboswitch</scene> operates by the binding of a guanine, hypoxanthine, or xanthine to the aptamer domain. Through allosteric effects the aptamer then changes the conformation of the expression platform which results in the premature termination of transcription. Thus, the guanine riboswitch has two distinct conformations in which it operates: a metabolite bound and metabolite-free folds, involving the alternative base-pairing of the regulatory RNA region.<ref>PMID: 15610857 </ref>
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| == Riboswitch Structure == | | == Structure == |
| The guanine riboswitch is comprised of three helices which are labeled P1, P2, and P3 which connect to form a junction. It is within this junction that ligand binding occurs. When the g-riboswitch-guanine complex is formed the kissing interactions of two hairpin loops force P2 and P3 to align in a parallel fashion and form hydrogen bonds. The <scene name='Sandbox_Reserved_402/Binding_site/2'>ligand</scene> is bound to the junction within the guanine riboswitch via several hydrogen bonds to nucleotides U22, U47, U51, C74. Due to the compactness of the binding site the ligand must utilize the induced-fit binding mechanism. <ref>PMID: 17175531 </ref>
| | The <scene name='Sandbox_Reserved_387/Head_module/1'>head module</scene> of mediator from ''S.cerevisiae'' is made of seven subunits which are Med22(Srb6), Med20(Srb2), Med18(Srb5), Med17(Srb4), Med11, Med6, and Med8.<ref name="nature" /> Of these subunits, Med11, Med17(Srb4), and Med22(Srb6) make the mini-head of the head module. The subunits of the core-head plus the subunits of the mini-head are what make up full head structure. The structure shows the three domains: the neck, which is shown by pink helices, the fixed jaw, which is shown by mostly pink helices and a few yellow beta sheets, and the movable jaw, which is shown by mostly yellow beta sheets and a few pink helices. |
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| == Regulation Mechanism ==
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| Metabolite-binding riboswitches are triggered if a high concentration of the metabolite is present within the cell. Under these conditions, the metabolite will interact with the aptamer domain, with high affinity and selectivity, which will then stabilize the metabolite bound fold in the nascent RNA, and in so doing prevents the formation of the metabolite-free fold. This typically results in the stabilization or disruption of a regulatory hairpin, which prematurely terminates transcription or sequesters the ribosome-binding site, thereby regulating gene expression. In the absence of the metabolite when the 5’-UTR is transcribed the riboswitch folds into the metabolite-free fold which does not interfere with the expression of the adjacent open reading frame.
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| In Bacillus subtilis, the 5'-UTR of xpt-pbuX mRNA binds guanine with high precision to down regulate the expression of genes by forming transcription terminator structures. Due to the mechanism and function of riboswitches, they are an attractive target for drug development. <ref>PMID: 15610857 </ref>
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