5g4x: Difference between revisions
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==The crystal structure of the SHANK3 N-terminus== | ==The crystal structure of the SHANK3 N-terminus== | ||
<StructureSection load='5g4x' size='340' side='right' caption='[[5g4x]], [[Resolution|resolution]] 2.17Å' scene=''> | <StructureSection load='5g4x' size='340' side='right'caption='[[5g4x]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5g4x]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5g4x]] is a 1 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=5G4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G4X FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.166Å</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=EDO:1,2-ETHANEDIOL'>EDO</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=5g4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g4x OCA], [https://pdbe.org/5g4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g4x RCSB], [https://www.ebi.ac.uk/pdbsum/5g4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g4x 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 5g4x" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5g4x" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Shank protein|Shank protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Barsukov | [[Category: Barsukov I]] | ||
[[Category: Zacharchenko | [[Category: Zacharchenko T]] | ||
Latest revision as of 16:39, 26 July 2023
The crystal structure of the SHANK3 N-terminusThe crystal structure of the SHANK3 N-terminus
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 PubMedSHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes. SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras.,Lilja J, Zacharchenko T, Georgiadou M, Jacquemet G, Franceschi N, Peuhu E, Hamidi H, Pouwels J, Martens V, Nia FH, Beifuss M, Boeckers T, Kreienkamp HJ, Barsukov IL, Ivaska J Nat Cell Biol. 2017 Mar 6. doi: 10.1038/ncb3487. PMID:28263956[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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