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| | <StructureSection load='6bd1' size='340' side='right'caption='[[6bd1]], [[Resolution|resolution]] 2.35Å' scene=''> | | <StructureSection load='6bd1' size='340' side='right'caption='[[6bd1]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bd1]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BD1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BD1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bd1]] is a 8 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=6BD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BD1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 2.35Å</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=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=6bd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bd1 OCA], [http://pdbe.org/6bd1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bd1 RCSB], [http://www.ebi.ac.uk/pdbsum/6bd1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bd1 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=6bd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bd1 OCA], [https://pdbe.org/6bd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bd1 RCSB], [https://www.ebi.ac.uk/pdbsum/6bd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bd1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/1433T_BOVIN 1433T_BOVIN]] 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. Negatively regulates the kinase activity of PDPK1 (By similarity). | + | [https://www.uniprot.org/uniprot/1433T_HUMAN 1433T_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. Negatively regulates the kinase activity of PDPK1.<ref>PMID:12177059</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__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dominguez, R]] | + | [[Category: Dominguez R]] |
| - | [[Category: Kast, D J]] | + | [[Category: Kast DJ]] |
| - | [[Category: Cell motility]]
| + | |
| - | [[Category: Cytoskeleton regulation]]
| + | |
| - | [[Category: Phosphate binding protein]]
| + | |
| - | [[Category: Protein complex]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
1433T_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. Negatively regulates the kinase activity of PDPK1.[1]
Publication Abstract from PubMed
Filopodia are precursors of dendritic spines and polarized cell migration. The I-BAR-domain protein IRSp53 is a key regulator of filopodia dynamics that couples Rho-GTPase signaling to cytoskeleton and membrane remodeling, playing essential roles in neuronal development and cell motility. Here, we describe the structural-functional basis for 14-3-3-dependent inhibition of IRSp53. Phosphoproteomics, quantitative binding and crystallographic studies demonstrate that 14-3-3 binds to two pairs of phosphorylation sites in IRSp53. Using bicistronic expression, we obtain an IRSp53 heterodimer in which only one subunit is phosphorylated, and show that each subunit of IRSp53 independently binds one 14-3-3 dimer. A FRET-sensor assay using natively phosphorylated IRSp53 reveals opposite conformational changes upon binding of activatory (Cdc42, Eps8) or inhibitory (14-3-3) inputs. Finally, we show that 14-3-3 inhibits IRSp53 binding to membranes. Collectively, our findings support a mechanism whereby phosphorylation-dependent inhibition of IRSp53 by 14-3-3 counters membrane binding and interactions with Cdc42 and downstream cytoskeletal effectors.
Mechanism of IRSp53 inhibition by 14-3-3.,Kast DJ, Dominguez R Nat Commun. 2019 Jan 29;10(1):483. doi: 10.1038/s41467-019-08317-8. PMID:30696821[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sato S, Fujita N, Tsuruo T. Regulation of kinase activity of 3-phosphoinositide-dependent protein kinase-1 by binding to 14-3-3. J Biol Chem. 2002 Oct 18;277(42):39360-7. Epub 2002 Aug 12. PMID:12177059 doi:http://dx.doi.org/10.1074/jbc.M205141200
- ↑ Kast DJ, Dominguez R. Mechanism of IRSp53 inhibition by 14-3-3. Nat Commun. 2019 Jan 29;10(1):483. doi: 10.1038/s41467-019-08317-8. PMID:30696821 doi:http://dx.doi.org/10.1038/s41467-019-08317-8
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