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4yru

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Revision as of 13:21, 10 May 2017

Crystal structure of C-terminally truncated Neuronal Calcium Sensor (NCS-1) from Rattus norvegicus

Structural highlights

4yru is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yru"

@@ Line 1: / Line 1: @@
 ==Crystal structure of C-terminally truncated Neuronal Calcium Sensor (NCS-1) from Rattus norvegicus==
 <StructureSection load='4yru' size='340' side='right' caption='[[4yru]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4yru]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YRU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YRU 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></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=4yru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yru OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yru RCSB], [http://www.ebi.ac.uk/pdbsum/4yru 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=4yru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yru OCA], [http://pdbe.org/4yru PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yru RCSB], [http://www.ebi.ac.uk/pdbsum/4yru PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yru ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4yru" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4yru

From Proteopedia

Revision as of 13:21, 10 May 2017

Crystal structure of C-terminally truncated Neuronal Calcium Sensor (NCS-1) from Rattus norvegicus

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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