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| | ==Structure of two-domain translational regulator Yih1 reveals a possible mechanism of action== | | ==Structure of two-domain translational regulator Yih1 reveals a possible mechanism of action== |
| - | <StructureSection load='6bqi' size='340' side='right' caption='[[6bqi]], [[NMR_Ensembles_of_Models | 3 NMR models]]' scene=''> | + | <StructureSection load='6bqi' size='340' side='right'caption='[[6bqi]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bqi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BQI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BQI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bqi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BQI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YIH1, YCR059C, YCR59C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bqi OCA], [https://pdbe.org/6bqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bqi RCSB], [https://www.ebi.ac.uk/pdbsum/6bqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bqi ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bqi OCA], [http://pdbe.org/6bqi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bqi RCSB], [http://www.ebi.ac.uk/pdbsum/6bqi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bqi ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/YIH1_YEAST YIH1_YEAST]] Translational regulator that ensures constant high levels of translation under amino acid starvation. Plays a role as a negative regulator of the GCN2 kinase activity; impairs GCN1-mediated GCN2 activation, and hence GCN2-mediated eIF-2-alpha phosphorylation in amino acid-starved cells and subsequent down-regulation of protein synthesis (PubMed:15126500, PubMed:15937339, PubMed:24333428). In normal conditions, it resides in a actin complex and has no activity (PubMed:15126500).<ref>PMID:15126500</ref> <ref>PMID:15937339</ref> <ref>PMID:24333428</ref> | + | [https://www.uniprot.org/uniprot/YIH1_YEAST YIH1_YEAST] Translational regulator that ensures constant high levels of translation under amino acid starvation. Plays a role as a negative regulator of the GCN2 kinase activity; impairs GCN1-mediated GCN2 activation, and hence GCN2-mediated eIF-2-alpha phosphorylation in amino acid-starved cells and subsequent down-regulation of protein synthesis (PubMed:15126500, PubMed:15937339, PubMed:24333428). In normal conditions, it resides in a actin complex and has no activity (PubMed:15126500).<ref>PMID:15126500</ref> <ref>PMID:15937339</ref> <ref>PMID:24333428</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Yeast impact homolog 1 (Yih1), or IMPACT in mammals, is part of a conserved regulatory module controlling the activity of General Control Nonderepressible 2 (Gcn2), a protein kinase that regulates protein synthesis. Yih1/IMPACT is implicated not only in many essential cellular processes, such as neuronal development, immune system regulation and the cell cycle, but also in cancer. Gcn2 must bind to Gcn1 in order to impair the initiation of protein translation. Yih1 hinders this key Gcn1-Gcn2 interaction by binding to Gcn1, thus preventing Gcn2-mediated inhibition of protein synthesis. Here, we solved the structures of the two domains of Saccharomyces cerevisiae Yih1 separately using Nuclear Magnetic Resonance and determined the relative positions of the two domains using a range of biophysical methods. Our findings support a compact structural model of Yih1 in which the residues required for Gcn1 binding are buried in the interface. This model strongly implies that Yih1 undergoes a large conformational rearrangement from a latent closed state to a primed open state to bind Gcn1. Our study provides structural insight into the interactions of Yih1 with partner molecules. |
| | + | |
| | + | Experimentally based structural model of Yih1 provides insight into its function in controlling the key translational regulator Gcn2.,Harjes E, Jameson GB, Tu YH, Burr N, Loo TS, Goroncy AK, Edwards PJB, Harjes S, Munro B, Gobl C, Sattlegger E, Norris GE FEBS Lett. 2021 Feb;595(3):324-340. doi: 10.1002/1873-3468.13990. Epub 2020 Nov, 22. PMID:33156522<ref>PMID:33156522</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6bqi" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | + | [[Category: Large Structures]] |
| - | [[Category: Edwards, P J.B]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Goroncy, A K]] | + | [[Category: Edwards PJB]] |
| - | [[Category: Harjes, E]] | + | [[Category: Goroncy AK]] |
| - | [[Category: Jameson, G B]] | + | [[Category: Harjes E]] |
| - | [[Category: Loo, T]] | + | [[Category: Jameson GB]] |
| - | [[Category: Norris, G E]] | + | [[Category: Loo T]] |
| - | [[Category: Sax]]
| + | [[Category: Norris GE]] |
| - | [[Category: Translation]]
| + | |
| - | [[Category: Translational regulation]]
| + | |
| Structural highlights
Function
YIH1_YEAST Translational regulator that ensures constant high levels of translation under amino acid starvation. Plays a role as a negative regulator of the GCN2 kinase activity; impairs GCN1-mediated GCN2 activation, and hence GCN2-mediated eIF-2-alpha phosphorylation in amino acid-starved cells and subsequent down-regulation of protein synthesis (PubMed:15126500, PubMed:15937339, PubMed:24333428). In normal conditions, it resides in a actin complex and has no activity (PubMed:15126500).[1] [2] [3]
Publication Abstract from PubMed
Yeast impact homolog 1 (Yih1), or IMPACT in mammals, is part of a conserved regulatory module controlling the activity of General Control Nonderepressible 2 (Gcn2), a protein kinase that regulates protein synthesis. Yih1/IMPACT is implicated not only in many essential cellular processes, such as neuronal development, immune system regulation and the cell cycle, but also in cancer. Gcn2 must bind to Gcn1 in order to impair the initiation of protein translation. Yih1 hinders this key Gcn1-Gcn2 interaction by binding to Gcn1, thus preventing Gcn2-mediated inhibition of protein synthesis. Here, we solved the structures of the two domains of Saccharomyces cerevisiae Yih1 separately using Nuclear Magnetic Resonance and determined the relative positions of the two domains using a range of biophysical methods. Our findings support a compact structural model of Yih1 in which the residues required for Gcn1 binding are buried in the interface. This model strongly implies that Yih1 undergoes a large conformational rearrangement from a latent closed state to a primed open state to bind Gcn1. Our study provides structural insight into the interactions of Yih1 with partner molecules.
Experimentally based structural model of Yih1 provides insight into its function in controlling the key translational regulator Gcn2.,Harjes E, Jameson GB, Tu YH, Burr N, Loo TS, Goroncy AK, Edwards PJB, Harjes S, Munro B, Gobl C, Sattlegger E, Norris GE FEBS Lett. 2021 Feb;595(3):324-340. doi: 10.1002/1873-3468.13990. Epub 2020 Nov, 22. PMID:33156522[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sattlegger E, Swanson MJ, Ashcraft EA, Jennings JL, Fekete RA, Link AJ, Hinnebusch AG. YIH1 is an actin-binding protein that inhibits protein kinase GCN2 and impairs general amino acid control when overexpressed. J Biol Chem. 2004 Jul 16;279(29):29952-62. Epub 2004 May 4. PMID:15126500 doi:http://dx.doi.org/10.1074/jbc.M404009200
- ↑ Pereira CM, Sattlegger E, Jiang HY, Longo BM, Jaqueta CB, Hinnebusch AG, Wek RC, Mello LE, Castilho BA. IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation. J Biol Chem. 2005 Aug 5;280(31):28316-23. doi: 10.1074/jbc.M408571200. Epub 2005 , Jun 2. PMID:15937339 doi:http://dx.doi.org/10.1074/jbc.M408571200
- ↑ Cambiaghi TD, Pereira CM, Shanmugam R, Bolech M, Wek RC, Sattlegger E, Castilho BA. Evolutionarily conserved IMPACT impairs various stress responses that require GCN1 for activating the eIF2 kinase GCN2. Biochem Biophys Res Commun. 2014 Jan 10;443(2):592-7. doi:, 10.1016/j.bbrc.2013.12.021. Epub 2013 Dec 11. PMID:24333428 doi:http://dx.doi.org/10.1016/j.bbrc.2013.12.021
- ↑ Harjes E, Jameson GB, Tu YH, Burr N, Loo TS, Goroncy AK, Edwards PJB, Harjes S, Munro B, Göbl C, Sattlegger E, Norris GE. Experimentally based structural model of Yih1 provides insight into its function in controlling the key translational regulator Gcn2. FEBS Lett. 2021 Feb;595(3):324-340. PMID:33156522 doi:10.1002/1873-3468.13990
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