Summary for 5AEQ
| Entry DOI | 10.2210/pdb5aeq/pdb |
| Related | 5AER |
| Descriptor | NEURONAL CALCIUM SENSOR 1, CALCIUM ION, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | signaling protein, calcium sensor |
| Biological source | RATTUS NORVEGICUS (NORWAY RAT) |
| Cellular location | Golgi apparatus, Golgi stack membrane; Peripheral membrane protein: P62168 |
| Total number of polymer chains | 2 |
| Total formula weight | 44091.78 |
| Authors | Saleem, M.,Karuppiah, V.,Pandalaneni, S.,Burgoyne, R.,Derrick, J.P.,Lian, L.Y. (deposition date: 2015-01-08, release date: 2015-02-18, Last modification date: 2024-01-10) |
| Primary citation | Pandalaneni, S.,Karuppiah, V.,Saleem, M.,Haynes, L.P.,Burgoyne, R.D.,Mayans, O.,Derrick, J.P.,Lian, L. 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., 290:18744-, 2015 Cited by 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. PubMed: 25979333DOI: 10.1074/JBC.M114.627059 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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