The C-terminal tail of human neuronal calcium sensor 1 regulates the conformational stability of the Ca2+-activated state

Pétur O. Heidarsson, Ida J. Bjerrum-Bohr, Gitte A. Jensen, Olaf Pongs, Bryan E. Finn, Flemming M. Poulsen, Birthe B. Kragelund*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


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 Ca2+-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.

Original languageEnglish
Pages (from-to)51-64
Number of pages14
JournalJournal of Molecular Biology
Issue number1-2
Publication statusPublished - 16 Mar 2012

Bibliographical note

Funding Information:
This work was supported by the Carlsberg Foundation and The Danish Council for Independent Research | Natural Sciences (B.B.K.) and the Swedish Foundation for Strategic Research (B.E.F.) . We thank the Knut and Alice Wallenberg Foundation for generously providing funds for the purchase of the Varian UNITYplus 600-MHz spectrometer in Lund and The John and Birthe Meyer Foundation for the establishment of SBiNLab.

Other keywords

  • calcium binding
  • membrane interaction
  • NCS-1
  • NMR
  • protein stability


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