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| | ==Spinophilin PDZ domain== | | ==Spinophilin PDZ domain== |
| - | <StructureSection load='2g5m' size='340' side='right' caption='[[2g5m]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2g5m' size='340' side='right'caption='[[2g5m]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2g5m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G5M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2G5M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2g5m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G5M FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fn5|2fn5]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ppp1r9b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=2g5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g5m OCA], [https://pdbe.org/2g5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g5m RCSB], [https://www.ebi.ac.uk/pdbsum/2g5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g5m ProSAT]</span></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=2g5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g5m OCA], [http://pdbe.org/2g5m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2g5m RCSB], [http://www.ebi.ac.uk/pdbsum/2g5m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2g5m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NEB2_RAT NEB2_RAT]] Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration (By similarity).<ref>PMID:15743906</ref> <ref>PMID:15793568</ref> | + | [https://www.uniprot.org/uniprot/NEB2_RAT NEB2_RAT] Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration (By similarity).<ref>PMID:15743906</ref> <ref>PMID:15793568</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Kelker, M S]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Peti, W]] | + | [[Category: Kelker MS]] |
| - | [[Category: Cn]] | + | [[Category: Peti W]] |
| - | [[Category: Pdz domain]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Spinophilin]]
| + | |
| - | [[Category: Synaptic transmission]]
| + | |
| Structural highlights
Function
NEB2_RAT Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration (By similarity).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Neurabin and spinophilin are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. However, thus far, it is still unknown how neurabin and spinophilin themselves are targeted to these membrane receptors. Spinophilin and neurabin contain a single PDZ domain, a common protein-protein interaction recognition motif, which are 86% identical in sequence. We report the structures of both the neurabin and spinophilin PDZ domains determined using biomolecular NMR spectroscopy. These proteins form the canonical PDZ domain fold. However, despite their high degree of sequence identity, there are distinct and significant structural differences between them, especially between the peptide binding pockets. Using two-dimensional 1H-15N HSQC NMR analysis, we demonstrate that C-terminal peptide ligands derived from glutamatergic AMPA and NMDA receptors and cytosolic proteins directly and differentially bind spinophilin and neurabin PDZ domains. This peptide binding data also allowed us to classify the neurabin and spinophilin PDZ domains as the first identified neuronal hybrid class V PDZ domains, which are capable of binding both class I and II peptides. Finally, the ability to bind to glutamate receptor subunits suggests that the PDZ domains of neurabin and spinophilin are important for targeting PP1 to C-terminal phosphorylation sites in AMPA and NMDA receptor subunits.
Structural basis for spinophilin-neurabin receptor interaction.,Kelker MS, Dancheck B, Ju T, Kessler RP, Hudak J, Nairn AC, Peti W Biochemistry. 2007 Mar 6;46(9):2333-44. Epub 2007 Feb 6. PMID:17279777[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Terry-Lorenzo RT, Roadcap DW, Otsuka T, Blanpied TA, Zamorano PL, Garner CC, Shenolikar S, Ehlers MD. Neurabin/protein phosphatase-1 complex regulates dendritic spine morphogenesis and maturation. Mol Biol Cell. 2005 May;16(5):2349-62. Epub 2005 Mar 2. PMID:15743906 doi:10.1091/mbc.E04-12-1054
- ↑ Wang X, Zeng W, Soyombo AA, Tang W, Ross EM, Barnes AP, Milgram SL, Penninger JM, Allen PB, Greengard P, Muallem S. Spinophilin regulates Ca2+ signalling by binding the N-terminal domain of RGS2 and the third intracellular loop of G-protein-coupled receptors. Nat Cell Biol. 2005 Apr;7(4):405-11. Epub 2005 Mar 27. PMID:15793568 doi:10.1038/ncb1237
- ↑ Kelker MS, Dancheck B, Ju T, Kessler RP, Hudak J, Nairn AC, Peti W. Structural basis for spinophilin-neurabin receptor interaction. Biochemistry. 2007 Mar 6;46(9):2333-44. Epub 2007 Feb 6. PMID:17279777 doi:10.1021/bi602341c
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