View source for 5izu


==A new binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function==
<StructureSection load='5izu' size='340' side='right'caption='[[5izu]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5izu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IZU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.494&#8491;</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=5izu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5izu OCA], [https://pdbe.org/5izu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5izu RCSB], [https://www.ebi.ac.uk/pdbsum/5izu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5izu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SHAN3_MOUSE SHAN3_MOUSE] Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. 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. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation.<ref>PMID:21423165</ref> <ref>PMID:21558424</ref> <ref>PMID:23739967</ref> <ref>PMID:24153177</ref> 
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== Publication Abstract from PubMed ==
Shank and SAPAP (synapse-associated protein 90/postsynaptic density-95-associated protein) are two highly abundant scaffold proteins that directly interact with each other to regulate excitatory synapse development and plasticity. Mutations of SAPAP, but not other reported Shank PDZ domain binders, share a significant overlap on behavioral abnormalities with the mutations of Shank both in patients and in animal models. The molecular mechanism governing the exquisite specificity of the Shank/SAPAP interaction is not clear, however. Here we report that a sequence preceding the canonical PDZ domain of Shank, together with the elongated PDZ BC loop, form another binding site for a sequence upstream of the SAPAP PDZ-binding motif, leading to a several hundred-fold increase in the affinity of the Shank/SAPAP interaction. We provide evidence that the specific interaction afforded by this newly identified site is required for Shank synaptic targeting and the Shank-induced synaptic activity increase. Our study provides a molecular explanation of how Shank and SAPAP dosage changes due to their gene copy number variations can contribute to different psychiatric disorders.

A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function.,Zeng M, Shang Y, Guo T, He Q, Yung WH, Liu K, Zhang M Proc Natl Acad Sci U S A. 2016 May 16. pii: 201523265. PMID:27185935<ref>PMID:27185935</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5izu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Shank protein|Shank protein]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Shang Y]]
[[Category: Zeng M]]
[[Category: Zhang M]]