5o99: Difference between revisions
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==Unconventional SH3 domain from the postsynaptic density scaffold protein Shank3== | ==Unconventional SH3 domain from the postsynaptic density scaffold protein Shank3== | ||
<StructureSection load='5o99' size='340' side='right' caption='[[5o99]], [[Resolution|resolution]] 0.87Å' scene=''> | <StructureSection load='5o99' size='340' side='right'caption='[[5o99]], [[Resolution|resolution]] 0.87Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5o99]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O99 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5o99]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O99 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</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]] 0.871Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</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=5o99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o99 OCA], [https://pdbe.org/5o99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o99 RCSB], [https://www.ebi.ac.uk/pdbsum/5o99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o99 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/SHAN3_RAT SHAN3_RAT] Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and Homer, respectively, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5o99" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5o99" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Shank protein|Shank protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rattus norvegicus]] | ||
[[Category: | [[Category: Boeckers TM]] | ||
[[Category: | [[Category: Kursula P]] | ||
[[Category: | [[Category: Myllykoski M]] | ||
[[Category: | [[Category: Ponna SK]] | ||
Latest revision as of 12:37, 6 December 2023
Unconventional SH3 domain from the postsynaptic density scaffold protein Shank3Unconventional SH3 domain from the postsynaptic density scaffold protein Shank3
Structural highlights
FunctionSHAN3_RAT Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and Homer, respectively, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction. Publication Abstract from PubMedThe Shank family comprises three large multi-domain proteins playing central roles as protein scaffolds in the neuronal postsynaptic density. The Shank proteins are closely linked to neuropsychiatric diseases, such as autism spectrum disorders. One characteristic domain in the Shank family is the SH3 domain, assumed to play a role in protein-protein interactions; however, no specific ligand binding to any Shank SH3 domain has been described. We solved the crystal structure of the SH3 domain from Shank3 at sub-atomic resolution. While the structure presents the canonical SH3 domain fold, the binding site for proline-rich peptides is not conserved. In line with this, no binding of Pro-rich sequences by the Shank3 SH3 domain was observed. Sequence comparisons indicate that all Shank isoforms have similarly lost the classical Pro-rich peptide binding site from the SH3 domain. Whether the corresponding site in the Shank SH3 domains has evolved to bind a non-poly-Pro target sequence is currently not known. Our work provides an intriguing example of the evolution of a well-characterized protein-protein interaction domain within the context of multi-domain protein scaffolds, allowing the conservation of structural features, but losing canonical functional sites. The data are further discussed in light of known mutations in the SH3 domain or its vicinity in the different Shank isoforms. Structure of an unconventional SH3 domain from the postsynaptic density protein Shank3 at ultrahigh resolution.,Ponna SK, Myllykoski M, Boeckers TM, Kursula P Biochem Biophys Res Commun. 2017 Aug 26;490(3):806-812. doi:, 10.1016/j.bbrc.2017.06.121. Epub 2017 Jun 21. PMID:28647360[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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