5AER

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.221 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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, L.P.Burgoyne, R.D.Mayans, O.Derrick, J.P.Lian, L.

(2015) J Biol Chem 290: 18744

  • DOI: https://doi.org/10.1074/jbc.M114.627059
  • Primary Citation of Related Structures:  
    4YRU, 5AEQ, 5AER, 5AFP

  • PubMed Abstract: 

    Neuronal calcium sensor-1 (NCS-1) is the primordial member of the neuronal calcium sensor family of EF-hand Ca(2+)-binding proteins. It interacts with both the G-protein-coupled receptor (GPCR) dopamine D2 receptor (D2R), regulating its internalization and surface expression, and the cognate kinases GRK1 and GRK2. Determination of the crystal structures of Ca(2+)/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 Ca(2+)/NCS-1, but only one copy of the GRK1 peptide binds. The different binding modes are made possible by the C-lobe-binding site of NCS-1, which adopts alternative conformations in each complex. C-terminal residues Ser-178-Val-190 act in concert with the flexible EF3/EF4 loop region to effectively form different peptide-binding sites. In the Ca(2+)/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 α-helix. Removal of Ser-178-Val-190 generated a C-terminal truncation mutant that 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 ramifications for the target specificity and diversity of NCS-1.


  • Organizational Affiliation

    From the NMR Centre for Structural Biology, Institute of Integrative Biology, and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NEURONAL CALCIUM SENSOR 1190Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for P62168 (Rattus norvegicus)
Explore P62168 
Go to UniProtKB:  P62168
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62168
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
D(2) DOPAMINE RECEPTOR
B, C
14Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for P14416 (Homo sapiens)
Explore P14416 
Go to UniProtKB:  P14416
PHAROS:  P14416
GTEx:  ENSG00000149295 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP14416
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.221 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.67α = 90
b = 44.67β = 90
c = 205.52γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-02-18
    Type: Initial release
  • Version 1.1: 2015-06-03
    Changes: Database references
  • Version 1.2: 2015-08-05
    Changes: Database references
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description