2lcp

NMR structure of calcium loaded, un-myristoylated human NCS-1

spinqualitylabelsall models 2lcp Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2lcp is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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