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| | <SX load='5grs' size='340' side='right' viewer='molstar' caption='[[5grs]], [[Resolution|resolution]] 5.40Å' scene=''> | | <SX load='5grs' size='340' side='right' viewer='molstar' caption='[[5grs]], [[Resolution|resolution]] 5.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5grs]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Fission_yeast Fission yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GRS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GRS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5grs]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GRS FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yhc|4yhc]], [[5gpd|5gpd]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">scp1, SPBC3B9.15c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284812 Fission yeast]), sre1, SPBC19C2.09 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284812 Fission yeast])</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=5grs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5grs OCA], [https://pdbe.org/5grs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5grs RCSB], [https://www.ebi.ac.uk/pdbsum/5grs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5grs 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=5grs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5grs OCA], [http://pdbe.org/5grs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5grs RCSB], [http://www.ebi.ac.uk/pdbsum/5grs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5grs ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SCAP_SCHPO SCAP_SCHPO]] Escort protein required for sre1 processing at low sterol as well as oxygen levels. May regulate export of the scp1/sre1 complex from the ER at low sterol or oxygen levels. 4-methyl sterols bound to scp1 may mask an ER-export signal in scp1 leading to retention of the complex in the ER. Release of 4-methyl sterols may trigger a conformational change in the SSC domain of scp1 unmasking the ER export signal leading to recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of sre1 in the Golgi, release of the transcription factor fragment of sre1 from the membrane, its import into the nucleus and up-regulation of genes required for ergosterol biosynthesis as well as anaerobic growth.[UniProtKB:P97260]<ref>PMID:15797383</ref> <ref>PMID:17595166</ref> [[http://www.uniprot.org/uniprot/SREBP_SCHPO SREBP_SCHPO]] Transcriptional activator required for transcription of genes required for adaptation to anaerobic growth like those implicated in the nonrespiratory oxygen-consumptive biosynthetic pathways of sterol, heme, sphingolipid, and ubiquinone biosynthesis. May monitor oxygen levels through sterol synthesis steps which require oxygen.<ref>PMID:15797383</ref> <ref>PMID:16537923</ref> <ref>PMID:18276645</ref> | + | [https://www.uniprot.org/uniprot/SCAP_SCHPO SCAP_SCHPO] Escort protein required for sre1 processing at low sterol as well as oxygen levels. May regulate export of the scp1/sre1 complex from the ER at low sterol or oxygen levels. 4-methyl sterols bound to scp1 may mask an ER-export signal in scp1 leading to retention of the complex in the ER. Release of 4-methyl sterols may trigger a conformational change in the SSC domain of scp1 unmasking the ER export signal leading to recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of sre1 in the Golgi, release of the transcription factor fragment of sre1 from the membrane, its import into the nucleus and up-regulation of genes required for ergosterol biosynthesis as well as anaerobic growth.[UniProtKB:P97260]<ref>PMID:15797383</ref> <ref>PMID:17595166</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Fission yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gong, X]] | + | [[Category: Schizosaccharomyces pombe 972h-]] |
| - | [[Category: Qian, H W]] | + | [[Category: Gong X]] |
| - | [[Category: Wu, J P]] | + | [[Category: Qian HW]] |
| - | [[Category: Yan, N]] | + | [[Category: Wu JP]] |
| - | [[Category: Protein complex]] | + | [[Category: Yan N]] |
| - | [[Category: Protein transport]]
| + | |
| Structural highlights
Function
SCAP_SCHPO Escort protein required for sre1 processing at low sterol as well as oxygen levels. May regulate export of the scp1/sre1 complex from the ER at low sterol or oxygen levels. 4-methyl sterols bound to scp1 may mask an ER-export signal in scp1 leading to retention of the complex in the ER. Release of 4-methyl sterols may trigger a conformational change in the SSC domain of scp1 unmasking the ER export signal leading to recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of sre1 in the Golgi, release of the transcription factor fragment of sre1 from the membrane, its import into the nucleus and up-regulation of genes required for ergosterol biosynthesis as well as anaerobic growth.[UniProtKB:P97260][1] [2]
Publication Abstract from PubMed
Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 A and cryo-EM structure of the complex at 5.4 A together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.
Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.,Gong X, Qian H, Shao W, Li J, Wu J, Liu JJ, Li W, Wang HW, Espenshade P, Yan N Cell Res. 2016 Nov;26(11):1197-1211. doi: 10.1038/cr.2016.123. Epub 2016 Nov 4. PMID:27811944[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hughes AL, Todd BL, Espenshade PJ. SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast. Cell. 2005 Mar 25;120(6):831-42. PMID:15797383 doi:http://dx.doi.org/10.1016/j.cell.2005.01.012
- ↑ Hughes AL, Lee CY, Bien CM, Espenshade PJ. 4-Methyl sterols regulate fission yeast SREBP-Scap under low oxygen and cell stress. J Biol Chem. 2007 Aug 17;282(33):24388-96. Epub 2007 Jun 26. PMID:17595166 doi:http://dx.doi.org/10.1074/jbc.M701326200
- ↑ Gong X, Qian H, Shao W, Li J, Wu J, Liu JJ, Li W, Wang HW, Espenshade P, Yan N. Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization. Cell Res. 2016 Nov;26(11):1197-1211. doi: 10.1038/cr.2016.123. Epub 2016 Nov 4. PMID:27811944 doi:http://dx.doi.org/10.1038/cr.2016.123
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