5ovc: Difference between revisions
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The | ==PDZ domain from rat Shank3 bound to the C terminus of GKAP== | ||
<StructureSection load='5ovc' size='340' side='right' caption='[[5ovc]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ovc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OVC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OVC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | |||
<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=5ovc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ovc OCA], [http://pdbe.org/5ovc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ovc RCSB], [http://www.ebi.ac.uk/pdbsum/5ovc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ovc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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;"> | |||
== Publication Abstract from PubMed == | |||
The Shank proteins are crucial scaffolding elements of the post-synaptic density (PSD). One of the best-characterized domains in Shank is the PDZ domain, which binds to C-terminal segments of several other PSD proteins. We carried out a detailed structural analysis of Shank3 PDZ domain-peptide complexes, in order to understand determinants of binding affinity towards different ligand proteins. Ligand peptides from four different proteins were cocrystallized with the Shank3 PDZ domain, and binding affinities were determined calorimetrically. In addition, to conserve class I interactions between the first and third C-terminal peptide residue and Shank3, side chain interactions of other residues in the peptide with the PDZ domain are important factors in defining affinity. Structural conservation suggests that the binding specificities of the PDZ domains from different Shanks are similar. Two conserved buried water molecules in PDZ domains may affect correct local folding of ligand recognition determinants. The solution structure of a tandem Shank3 construct containing the SH3 and PDZ domains showed that the two domains are close to each other, which could be of relevance, when recognizing and binding full target proteins. The SH3 domain did not affect the affinity of the PDZ domain towards short target peptides, and the schizophrenia-linked Shank3 mutation R536W in the linker between the domains had no effect on the structure or peptide interactions of the Shank3 SH3-PDZ unit. Our data show the spatial arrangement of two adjacent Shank domains and pinpoint affinity determinants for short PDZ domain ligands with limited sequence homology. This article is protected by copyright. All rights reserved. | |||
Structural basis for PDZ domain interactions in the post-synaptic density scaffolding protein Shank3.,Ponna SK, Ruskamo S, Myllykoski M, Keller C, Boeckers TM, Kursula P J Neurochem. 2018 Feb 23. doi: 10.1111/jnc.14322. PMID:29473168<ref>PMID:29473168</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: Boeckers, T | <div class="pdbe-citations 5ovc" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Boeckers, T M]] | |||
[[Category: Kursula, P]] | |||
[[Category: Myllykoski, M]] | [[Category: Myllykoski, M]] | ||
[[Category: | [[Category: Ponna, S K]] | ||
[[Category: C terminus]] | |||
[[Category: Pdz domain]] | |||
[[Category: Peptide binding]] | |||
[[Category: Post-synaptic density]] | |||
[[Category: Protein binding]] | |||
Revision as of 08:00, 8 March 2018
PDZ domain from rat Shank3 bound to the C terminus of GKAPPDZ domain from rat Shank3 bound to the C terminus of GKAP
Structural highlights
Function[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. Publication Abstract from PubMedThe Shank proteins are crucial scaffolding elements of the post-synaptic density (PSD). One of the best-characterized domains in Shank is the PDZ domain, which binds to C-terminal segments of several other PSD proteins. We carried out a detailed structural analysis of Shank3 PDZ domain-peptide complexes, in order to understand determinants of binding affinity towards different ligand proteins. Ligand peptides from four different proteins were cocrystallized with the Shank3 PDZ domain, and binding affinities were determined calorimetrically. In addition, to conserve class I interactions between the first and third C-terminal peptide residue and Shank3, side chain interactions of other residues in the peptide with the PDZ domain are important factors in defining affinity. Structural conservation suggests that the binding specificities of the PDZ domains from different Shanks are similar. Two conserved buried water molecules in PDZ domains may affect correct local folding of ligand recognition determinants. The solution structure of a tandem Shank3 construct containing the SH3 and PDZ domains showed that the two domains are close to each other, which could be of relevance, when recognizing and binding full target proteins. The SH3 domain did not affect the affinity of the PDZ domain towards short target peptides, and the schizophrenia-linked Shank3 mutation R536W in the linker between the domains had no effect on the structure or peptide interactions of the Shank3 SH3-PDZ unit. Our data show the spatial arrangement of two adjacent Shank domains and pinpoint affinity determinants for short PDZ domain ligands with limited sequence homology. This article is protected by copyright. All rights reserved. Structural basis for PDZ domain interactions in the post-synaptic density scaffolding protein Shank3.,Ponna SK, Ruskamo S, Myllykoski M, Keller C, Boeckers TM, Kursula P J Neurochem. 2018 Feb 23. doi: 10.1111/jnc.14322. PMID:29473168[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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