2LCP

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

Summary for 2LCP

• Entry DOI: 10.2210/pdb2lcp/pdb
• Related: 1fpw 1g8i 2ju0
• NMR Information: BMRB: 4378
• Descriptor: Neuronal calcium sensor 1, CALCIUM ION (2 entities in total)
• Functional Keywords: neuronal calcium sensor, ef-hand, calcium binding, metal binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus, Golgi stack membrane; Peripheral membrane protein: P62166
• Total number of polymer chains: 1
• Total formula weight: 22022.90

Authors

Heidarsson, P.O.,Bjerrum-Bohr, I.J.,Bellucci, L.,Gitte, J.,Corni, S.,Poulsen, F.M.,Finn, B.E.,Di Felice, R.,Kragelund, B. (deposition date: 2011-05-05, release date: 2012-02-01, Last modification date: 2024-05-15)

Primary citation

Heidarsson, P.O.,Bjerrum-Bohr, I.J.,Jensen, G.A.,Pongs, O.,Finn, B.E.,Poulsen, F.M.,Kragelund, B.B.
The C-terminal tail of human neuronal calcium sensor 1 regulates the conformational stability of the ca(2+)-activated state.
J.Mol.Biol., 417:51-64, 2012

PubMed Abstract: 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.

PubMed: 22227393
DOI: 10.1016/j.jmb.2011.12.049

Experimental method

SOLUTION NMR