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| | <StructureSection load='6t5h' size='340' side='right'caption='[[6t5h]], [[Resolution|resolution]] 2.04Å' scene=''> | | <StructureSection load='6t5h' size='340' side='right'caption='[[6t5h]], [[Resolution|resolution]] 2.04Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6t5h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T5H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6t5h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T5H FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.04Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STAR, STARD1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6t5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t5h OCA], [https://pdbe.org/6t5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t5h RCSB], [https://www.ebi.ac.uk/pdbsum/6t5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t5h ProSAT]</span></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=6t5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t5h OCA], [https://pdbe.org/6t5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t5h RCSB], [https://www.ebi.ac.uk/pdbsum/6t5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t5h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/STAR_HUMAN STAR_HUMAN] Non-classic congenital lipoid adrenal hyperplasia due to STAR deficency;Classic congenital lipoid adrenal hyperplasia due to STAR deficency;Familial glucocorticoid deficiency. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. | + | [https://www.uniprot.org/uniprot/STAR_HUMAN STAR_HUMAN] Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone.[https://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Antson, A A]] | + | [[Category: Antson AA]] |
| - | [[Category: Sluchanko, N N]] | + | [[Category: Sluchanko NN]] |
| - | [[Category: Titterington, J]] | + | [[Category: Titterington J]] |
| - | [[Category: Tugaeva, K V]] | + | [[Category: Tugaeva KV]] |
| - | [[Category: 14-3-3 protein]]
| + | |
| - | [[Category: Phosphopeptide-binding]]
| + | |
| - | [[Category: Protein chimera]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
STAR_HUMAN Non-classic congenital lipoid adrenal hyperplasia due to STAR deficency;Classic congenital lipoid adrenal hyperplasia due to STAR deficency;Familial glucocorticoid deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
STAR_HUMAN Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone.1433S_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
Publication Abstract from PubMed
Steroidogenesis in adrenals and gonads starts from cholesterol transport to mitochondria. This is mediated by the steroidogenic acute regulatory protein (STARD1), containing a mitochondrial import sequence followed by a cholesterol-binding START domain. Although mutations in this protein have been linked to lipoid congenital adrenal hyperplasia (LCAH), the mechanism of steroidogenesis regulation by STARD1 remains debatable. It has been hypothesized to involve a molten-globule structural transition and interaction with 14-3-3 proteins. In this study, we aimed to address the structural basis for the 14-3-3-STARD1 interaction. We show that, while the isolated START domain does not interact with 14-3-3, this interaction is enabled by STARD1 phosphorylation at Ser57, close to the mitochondrial peptide cleavage site. Biochemical analysis of the STARD1 affinity toward 14-3-3 and crystal structures of 14-3-3 complexes with Ser57 and Ser195 phosphopeptides suggest distinct roles of site-specific phosphorylations in recruiting 14-3-3, to modulate STARD1 activity, processing and import to the mitochondria. Phosphorylation at Ser195 creates a unique conditional site that could only bind to 14-3-3 upon partial unfolding of the START domain. Overall, our findings on the interaction between 14-3-3 and STARD1 may have potential clinical implications for patients with LCAH.
Molecular basis for the recognition of steroidogenic acute regulatory protein by the 14-3-3 protein family.,Tugaeva KV, Titterington J, Sotnikov DV, Maksimov EG, Antson AA, Sluchanko NN FEBS J. 2020 Sep;287(18):3944-3966. doi: 10.1111/febs.15474. Epub 2020 Aug 3. PMID:32633081[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tugaeva KV, Titterington J, Sotnikov DV, Maksimov EG, Antson AA, Sluchanko NN. Molecular basis for the recognition of steroidogenic acute regulatory protein by the 14-3-3 protein family. FEBS J. 2020 Sep;287(18):3944-3966. doi: 10.1111/febs.15474. Epub 2020 Aug 3. PMID:32633081 doi:http://dx.doi.org/10.1111/febs.15474
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