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Research article - Peer-reviewed, 2012

The C-Terminal Tail of Human Neuronal Calcium Sensor 1 Regulates the Conformational Stability of the Ca2+-Activated State

Heidarsson, Petur O.; Bjerrum-Bohr, Ida J.; Jensen, Gitte A.; Pongs, Olaf; Finn, Bryan; Poulsen, Flemming; Kragelund, Birthe B.


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. (C) 2012 Elsevier Ltd. All rights reserved.


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

Published in

Journal of Molecular Biology
2012, volume: 417, number: 1-2, pages: 51-64

Authors' information

Heidarsson, Petur O.
University of Copenhagen
Bjerrum-Bohr, Ida J.
University of Copenhagen
Jensen, Gitte A.
University of Copenhagen
Pongs, Olaf
University Medical Center, Hamburg-Eppendorf
Swedish University of Agricultural Sciences, Division of IT
Poulsen, Flemming
University of Copenhagen
Kragelund, Birthe B.
University of Copenhagen

UKÄ Subject classification

Biochemistry and Molecular Biology

Publication Identifiers


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