|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==CH2 chimera of human 14-3-3 sigma with the Gli1 phosphopeptide around Ser640== | | ==CH2 chimera of human 14-3-3 sigma with the Gli1 phosphopeptide around Ser640== |
| - | <StructureSection load='5om0' size='340' side='right' caption='[[5om0]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='5om0' size='340' side='right'caption='[[5om0]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5om0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OM0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5om0]] 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=5OM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OM0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 3.2Å</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=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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=5om0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5om0 OCA], [http://pdbe.org/5om0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5om0 RCSB], [http://www.ebi.ac.uk/pdbsum/5om0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5om0 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=5om0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5om0 OCA], [https://pdbe.org/5om0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5om0 RCSB], [https://www.ebi.ac.uk/pdbsum/5om0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5om0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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/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/GLI1_HUMAN GLI1_HUMAN] Acts as a transcriptional activator. May regulate the transcription of specific genes during normal development. May play a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling and thus cell proliferation and differentiation.<ref>PMID:10806483</ref> <ref>PMID:11238441</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5om0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5om0" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Antson, A A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Greive, S J]] | + | [[Category: Large Structures]] |
| - | [[Category: Sluchanko, N N]] | + | [[Category: Antson AA]] |
| - | [[Category: Tugaeva, K V]] | + | [[Category: Greive SJ]] |
| - | [[Category: 14-3-3 protein]] | + | [[Category: Sluchanko NN]] |
| - | [[Category: Phosphopeptide-binding]] | + | [[Category: Tugaeva KV]] |
| - | [[Category: Protein chimera]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
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.GLI1_HUMAN Acts as a transcriptional activator. May regulate the transcription of specific genes during normal development. May play a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling and thus cell proliferation and differentiation.[1] [2]
Publication Abstract from PubMed
In eukaryotes, several "hub" proteins integrate signals from different interacting partners that bind through intrinsically disordered regions. The 14-3-3 protein hub, which plays wide-ranging roles in cellular processes, has been linked to numerous human disorders and is a promising target for therapeutic intervention. Partner proteins usually bind via insertion of a phosphopeptide into an amphipathic groove of 14-3-3. Structural plasticity in the groove generates promiscuity allowing accommodation of hundreds of different partners. So far, accurate structural information has been derived for only a few 14-3-3 complexes with phosphopeptide-containing proteins and a variety of complexes with short synthetic peptides. To further advance structural studies, here we propose a novel approach based on fusing 14-3-3 proteins with the target partner peptide sequences. Such chimeric proteins are easy to design, express, purify and crystallize. Peptide attachment to the C terminus of 14-3-3 via an optimal linker allows its phosphorylation by protein kinase A during bacterial co-expression and subsequent binding at the amphipathic groove. Crystal structures of 14-3-3 chimeras with three different peptides provide detailed structural information on peptide-14-3-3 interactions. This simple but powerful approach, employing chimeric proteins, can reinvigorate studies of 14-3-3/phosphoprotein assemblies, including those with challenging low-affinity partners, and may facilitate the design of novel biosensors.
Chimeric 14-3-3 proteins for unraveling interactions with intrinsically disordered partners.,Sluchanko NN, Tugaeva KV, Greive SJ, Antson AA Sci Rep. 2017 Sep 20;7(1):12014. doi: 10.1038/s41598-017-12214-9. PMID:28931924[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Murone M, Luoh SM, Stone D, Li W, Gurney A, Armanini M, Grey C, Rosenthal A, de Sauvage FJ. Gli regulation by the opposing activities of fused and suppressor of fused. Nat Cell Biol. 2000 May;2(5):310-2. PMID:10806483 doi:10.1038/35010610
- ↑ Koyabu Y, Nakata K, Mizugishi K, Aruga J, Mikoshiba K. Physical and functional interactions between Zic and Gli proteins. J Biol Chem. 2001 Mar 9;276(10):6889-92. Epub 2001 Jan 12. PMID:11238441 doi:http://dx.doi.org/10.1074/jbc.C000773200
- ↑ Sluchanko NN, Tugaeva KV, Greive SJ, Antson AA. Chimeric 14-3-3 proteins for unraveling interactions with intrinsically disordered partners. Sci Rep. 2017 Sep 20;7(1):12014. doi: 10.1038/s41598-017-12214-9. PMID:28931924 doi:http://dx.doi.org/10.1038/s41598-017-12214-9
|
