2lcp

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.