5aer

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Revision as of 13:24, 10 May 2017

Neuronal calcium sensor-1 (NCS-1)from Rattus norvegicus complex with D2 dopamine receptor peptide from Homo sapiens

Structural highlights

5aer is a 3 chain structure. This structure supersedes the now removed PDB entry 2you. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5aeq
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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] [DRD2_HUMAN] Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Albizu L, Holloway T, Gonzalez-Maeso J, Sealfon SC. Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology. 2011 Sep;61(4):770-7. doi: 10.1016/j.neuropharm.2011.05.023., Epub 2011 May 27. PMID:21645528 doi:http://dx.doi.org/10.1016/j.neuropharm.2011.05.023
↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5aer"

@@ Line 1: / Line 1: @@
 ==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]] 2.19&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5aeq|5aeq]]</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://www.rcsb.org/pdb/explore.do?structureId=5aer RCSB], [http://www.ebi.ac.uk/pdbsum/5aer PDBsum]</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=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>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 5aer" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

5aer

From Proteopedia

Revision as of 13:24, 10 May 2017

Neuronal calcium sensor-1 (NCS-1)from Rattus norvegicus complex with D2 dopamine receptor peptide from Homo sapiens

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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