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| | ==NMR structure of calcium loaded, un-myristoylated human NCS-1== | | ==NMR structure of calcium loaded, un-myristoylated human NCS-1== |
| - | <StructureSection load='2lcp' size='340' side='right' caption='[[2lcp]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lcp' size='340' side='right'caption='[[2lcp]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lcp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LCP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lcp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LCP 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> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fpw|1fpw]], [[1g8i|1g8i]], [[2ju0|2ju0]]</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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCS1, FLUP, FREQ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2lcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lcp OCA], [https://pdbe.org/2lcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lcp RCSB], [https://www.ebi.ac.uk/pdbsum/2lcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lcp 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=2lcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lcp OCA], [http://pdbe.org/2lcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lcp RCSB], [http://www.ebi.ac.uk/pdbsum/2lcp PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCS1_HUMAN NCS1_HUMAN]] 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 (By similarity). Stimulates PI4KB kinase activity (By similarity). Involved in long-term synaptic plasticity through its interaction with PICK1 (By similarity). May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel (By similarity). | + | [https://www.uniprot.org/uniprot/NCS1_HUMAN NCS1_HUMAN] 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 (By similarity). Stimulates PI4KB kinase activity (By similarity). Involved in long-term synaptic plasticity through its interaction with PICK1 (By similarity). May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bellucci, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Bjerrum-Bohr, I J]] | + | [[Category: Bellucci L]] |
| - | [[Category: Corni, S]] | + | [[Category: Bjerrum-Bohr IJ]] |
| - | [[Category: Felice, R Di]] | + | [[Category: Corni S]] |
| - | [[Category: Finn, B E]] | + | [[Category: Di Felice R]] |
| - | [[Category: Gitte, J]] | + | [[Category: Finn BE]] |
| - | [[Category: Heidarsson, P O]] | + | [[Category: Gitte J]] |
| - | [[Category: Kragelund, B]] | + | [[Category: Heidarsson PO]] |
| - | [[Category: Poulsen, F M]] | + | [[Category: Kragelund B]] |
| - | [[Category: Calcium binding]]
| + | [[Category: Poulsen FM]] |
| - | [[Category: Ef-hand]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Neuronal calcium sensor]]
| + | |
| Structural highlights
Function
NCS1_HUMAN 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 (By similarity). Stimulates PI4KB kinase activity (By similarity). Involved in long-term synaptic plasticity through its interaction with PICK1 (By similarity). May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel (By similarity).
Publication Abstract from PubMed
Neuronal calcium sensor 1 (NCS-1) and orthologs are expressed in all organisms from yeast to humans. In the latter, NCS-1 plays an important role in neurotransmitter release and interacts with a plethora of binding partners mostly through a large solvent-exposed hydrophobic crevice. The structural basis behind the multispecific binding profile is not understood. To begin to address this, we applied NMR spectroscopy to determine the solution structure of calcium-bound human NCS-1. The structure in solution demonstrates interdomain flexibility and, in the absence of a binding partner, the C-terminal tail residues occupy the hydrophobic crevice as a ligand mimic. A variant with a C-terminal tail deletion shows lack of a defined structure but maintained cooperative unfolding and dramatically reduced global stability. The results suggest that the C-terminal tail is important for regulating the conformational stability of the Ca(2+)-activated state. Furthermore, a single amino acid mutation that was recently diagnosed in a patient with autistic spectrum disorder was seen to affect the C-terminal tail and binding crevice in NCS-1.
The C-Terminal Tail of Human Neuronal Calcium Sensor 1 Regulates the Conformational Stability of the Ca(2+)-Activated State.,Heidarsson PO, Bjerrum-Bohr IJ, Jensen GA, Pongs O, Finn BE, Poulsen FM, Kragelund BB J Mol Biol. 2011 Dec 29. PMID:22227393[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Heidarsson PO, Bjerrum-Bohr IJ, Jensen GA, Pongs O, Finn BE, Poulsen FM, Kragelund BB. The C-Terminal Tail of Human Neuronal Calcium Sensor 1 Regulates the Conformational Stability of the Ca(2+)-Activated State. J Mol Biol. 2011 Dec 29. PMID:22227393 doi:10.1016/j.jmb.2011.12.049
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