Molecular structure and target recognition of neuronal calcium sensor proteins.
BACKGROUND
Neuronal calcium sensor (NCS) proteins, a sub-branch of the calmodulin superfamily, are expressed in the brain and retina where they transduce calcium signals and are genetically linked to degenerative diseases. The amino acid sequences of NCS proteins are highly conserved but their physiological functions are quite distinct. Retinal recoverin and guanylate cyclase activating proteins (GCAPs) both serve as calcium sensors in retinal rod cells, neuronal frequenin (NCS1) modulate synaptic activity and neuronal secretion, K+ channel interacting proteins (KChIPs) regulate ion channels to control neuronal excitability, and DREAM (KChIP3) is a transcriptional repressor that regulates neuronal gene expression.


METHODS
Here we review the molecular structures of myristoylated forms of NCS1, recoverin, and GCAP1 that all look very different, suggesting that the sequestered myristoyl group helps to refold these highly homologous proteins into very different structures. The molecular structure of NCS target complexes have been solved for recoverin bound to rhodopsin kinase, NCS-1 bound to phosphatidylinositol 4-kinase, and KChIP1 bound to A-type K+ channels.


CONCLUSIONS
We propose the idea that N-terminal myristoylation is critical for shaping each NCS family member into a unique structure, which upon Ca2+-induced extrusion of the myristoyl group exposes a unique set of previously masked residues, thereby exposing a distinctive ensemble of hydrophobic residues to associate specifically with a particular physiological target. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling.
University of California, Davis Department of Chemistry, Davis, CA 95616, USa. ames@chem.ucdavis.edu
James B
JB
Ames
Sunghyuk
S
Lim
D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling; D002147:Calmodulin / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051580:Neuronal Calcium-Sensor Proteins / Q000737:chemistry*; D011485:Protein Binding; D046188:Protein Modification, Translational; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D002147:Calmodulin; D051580:Neuronal Calcium-Sensor Proteins