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| | ==Neuronal calcium sensor-1 (NCS-1)from Rattus norvegicus complex with D2 dopamine receptor peptide from Homo sapiens== | | ==Neuronal calcium sensor-1 (NCS-1)from Rattus norvegicus complex with D2 dopamine receptor peptide from Homo sapiens== |
| - | <StructureSection load='5aer' size='340' side='right' caption='[[5aer]], [[Resolution|resolution]] 2.19Å' scene=''> | + | <StructureSection load='5aer' size='340' side='right'caption='[[5aer]], [[Resolution|resolution]] 2.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5aer]] is a 3 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2you 2you]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AER OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AER FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5aer]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2you 2you]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AER FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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]] 2.19Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5aeq|5aeq]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=5aer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aer OCA], [http://pdbe.org/5aer PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5aer RCSB], [http://www.ebi.ac.uk/pdbsum/5aer PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5aer ProSAT]</span></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=5aer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aer OCA], [https://pdbe.org/5aer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5aer RCSB], [https://www.ebi.ac.uk/pdbsum/5aer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5aer ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/DRD2_HUMAN DRD2_HUMAN]] Myoclonic dystonia 11. The gene represented in this entry may be involved in disease pathogenesis. DRD2 mutations in myoclonic dystonia patients are rare, and their contribution to disease phenotype is unclear (PubMed:10716258). | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCS1_RAT NCS1_RAT]] Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin. Stimulates PI4KB kinase activity. Involved in long-term synaptic plasticity through its interaction with PICK1. May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel.<ref>PMID:17502602</ref> [[http://www.uniprot.org/uniprot/DRD2_HUMAN DRD2_HUMAN]] Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).<ref>PMID:21645528</ref> <ref>PMID:17264214</ref> | + | [https://www.uniprot.org/uniprot/NCS1_RAT NCS1_RAT] Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin. Stimulates PI4KB kinase activity. Involved in long-term synaptic plasticity through its interaction with PICK1. May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel.<ref>PMID:17502602</ref> |
| | <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 5aer" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5aer" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dopamine receptor 3D structures|Dopamine receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Burgoyne, R]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Derrick, J P]] | + | [[Category: Large Structures]] |
| - | [[Category: Karuppiah, V]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Lian, L Y]] | + | [[Category: Burgoyne R]] |
| - | [[Category: Pandalaneni, S]] | + | [[Category: Derrick JP]] |
| - | [[Category: Saleem, M]] | + | [[Category: Karuppiah V]] |
| - | [[Category: Dopamine receptor 2]] | + | [[Category: Lian LY]] |
| - | [[Category: Neuronal calcium sensor-1]] | + | [[Category: Pandalaneni S]] |
| - | [[Category: Signaling protein]] | + | [[Category: Saleem M]] |
| Structural highlights
Function
NCS1_RAT Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin. Stimulates PI4KB kinase activity. Involved in long-term synaptic plasticity through its interaction with PICK1. May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel.[1]
Publication Abstract from PubMed
Neuronal Calcium Sensor-1 (NCS-1) is the primordial member of the Neuronal Calcium Sensor (NCS) family of EF-hand Ca2+-binding proteins. It interacts with both the G-protein coupled receptor (GPCR) dopamine D2 receptor (D2R), regulating its internalisation and surface expression, and the cognate kinases, GRK1 and GRK2. Determination of the crystal structures of Ca2+/NCS-1 alone and in complex with peptides derived from D2R and GRK1 reveals that the differential recognition is facilitated by the conformational flexibility of the C-lobe binding site. We find that two copies of the D2R peptide bind within the hydrophobic crevice on Ca2+/NCS-1, but only one copy of the GRK1 peptide. The different binding modes are made possible by the C-lobe binding site of NCS-1, which adopts alternate conformations in each complex. C-terminal residues S178-V190 act in concert with the flexible EF3/EF4 loop region to effectively form different peptide binding sites. In the Ca2+/NCS-1-D2R peptide complex, the C-terminal region adopts a 310 helix-turn-310 helix, whereas in the GRK1 peptide complex it forms an alpha-helix. Removal of S178-V190 generated a C-terminal truncation mutant which formed a dimer, indicating that the NCS-1 C-terminal region prevents NCS-1 oligomerization. We propose that the flexible nature of the C-terminal region is essential to allow it to modulate its protein binding sites and adapt its conformation to accommodate both ligands. This appears to be driven by the variability of the conformation of the C-lobe binding site, which has ramification for the target specificity and diversity of NCS-1.
Neuronal Calcium Sensor-1 binds the D2 dopamine receptor and G-protein coupled receptor kinase 1 (GRK1) peptides using different modes of interactions.,Pandalaneni S, Karuppiah V, Saleem M, Haynes LP, Burgoyne RD, Mayans O, Derrick JP, Lian LY J Biol Chem. 2015 May 15. pii: jbc.M114.627059. PMID:25979333[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gambino F, Pavlowsky A, Begle A, Dupont JL, Bahi N, Courjaret R, Gardette R, Hadjkacem H, Skala H, Poulain B, Chelly J, Vitale N, Humeau Y. IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation. Proc Natl Acad Sci U S A. 2007 May 22;104(21):9063-8. Epub 2007 May 14. PMID:17502602 doi:http://dx.doi.org/10.1073/pnas.0701133104
- ↑ Pandalaneni S, Karuppiah V, Saleem M, Haynes LP, Burgoyne RD, Mayans O, Derrick JP, Lian LY. Neuronal Calcium Sensor-1 binds the D2 dopamine receptor and G-protein coupled receptor kinase 1 (GRK1) peptides using different modes of interactions. J Biol Chem. 2015 May 15. pii: jbc.M114.627059. PMID:25979333 doi:http://dx.doi.org/10.1074/jbc.M114.627059
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