4f7r

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==Crystal structure of 14-3-3 protein from Giardia intestinalis==
==Crystal structure of 14-3-3 protein from Giardia intestinalis==
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<StructureSection load='4f7r' size='340' side='right' caption='[[4f7r]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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<StructureSection load='4f7r' size='340' side='right'caption='[[4f7r]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4f7r]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Giain Giain]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F7R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F7R FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4f7r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Giardia_intestinalis Giardia intestinalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F7R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F7R FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<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=4f7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7r OCA], [http://pdbe.org/4f7r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f7r RCSB], [http://www.ebi.ac.uk/pdbsum/4f7r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7r ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4f7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7r OCA], [https://pdbe.org/4f7r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f7r RCSB], [https://www.ebi.ac.uk/pdbsum/4f7r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7r ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/1433_GIAIC 1433_GIAIC] 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 (By similarity). Binds with varying affinity to various synthetic phosphopeptides having a consensus binding motif RSX(pS/pT)XP, called mode-1, where X is any residue and pS/pT is a phosphorylated serine/threonine, and to synthetic phosphopeptides having a consensus binding motif Xp(S/T)X1-2-COOH, called mode-3, in which the phosphorylated residue occupies the penultimate C-terminal position in the target protein, but does not bind to their unphosphorylated counterparts (PubMed:19733174). Binds to synthetic human RAF1 phosphopeptides, but not to their unphosphorylated forms. Binds to difopein, a polypeptide containing a phosphorylation-independent binding motif (PubMed:16368691, PubMed:19733174). Involved in encystation (PubMed:19733174). Involved in cell proliferation. Required for actin and tubulin cytoskeletal organization. Regulates actin filament formation and nuclear size (PubMed:28932813).[UniProtKB:P62261]<ref>PMID:16368691</ref> <ref>PMID:19733174</ref> <ref>PMID:28932813</ref>
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The 14-3-3s are a family of dimeric evolutionary conserved pSer/pThr binding proteins that play a key role in multiple biological processes by interacting with a plethora of client proteins. Giardia duodenalis is a flagellated protozoan that affects millions of people worldwide causing an acute and chronic diarrheal disease. The single giardial 14-3-3 isoform (g14-3-3), unique in the 14-3-3 family, needs the constitutive phosphorylation of Thr214 and the polyglycylation of its C-terminus to be fully functional in vivo. Alteration of the phosphorylation and polyglycylation status affects the parasite differentiation into the cyst stage. To further investigate the role of these post-translational modifications, the crystal structure of the g14-3-3 was solved in the unmodified apo form. Oligomers of g14-3-3 were observed due to domain swapping events at the protein C-terminus. The formation of filaments was supported by TEM. Mutational analysis, in combination with native PAGE and chemical cross-linking, proved that polyglycylation prevents oligomerization. In silico phosphorylation and molecular dynamics simulations supported a structural role for the phosphorylation of Thr214 in promoting target binding. Our findings highlight unique structural features of g14-3-3 opening novel perspectives on the evolutionary history of this protein family and envisaging the possibility to develop anti-giardial drugs targeting g14-3-3.
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The Crystal Structure of Giardia duodenalis 14-3-3 in the Apo Form: When Protein Post-Translational Modifications Make the Difference.,Fiorillo A, di Marino D, Bertuccini L, Via A, Pozio E, Camerini S, Ilari A, Lalle M PLoS One. 2014 Mar 21;9(3):e92902. doi: 10.1371/journal.pone.0092902. eCollection, 2014. PMID:24658679<ref>PMID:24658679</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4f7r" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[14-3-3 protein|14-3-3 protein]]
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*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Giain]]
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[[Category: Giardia intestinalis]]
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[[Category: Fiorillo, A]]
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[[Category: Large Structures]]
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[[Category: Ilari, A]]
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[[Category: Fiorillo A]]
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[[Category: Lalle, M]]
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[[Category: Ilari A]]
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[[Category: 9-alpha-helix]]
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[[Category: Lalle M]]
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[[Category: Homodimer]]
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[[Category: Signal transduction]]
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[[Category: Signaling protein]]
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Current revision

Crystal structure of 14-3-3 protein from Giardia intestinalis

PDB ID 4f7r

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