4f7r
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<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> | <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> | ||
| - | </td></tr><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> | + | </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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=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> | <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> | ||
== Function == | == Function == | ||
[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> | [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> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4f7r" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Crystal structure of 14-3-3 protein from Giardia intestinalis
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