Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1.
Guanylate cyclase-activating proteins (GCAPs) are Ca(2+)-binding proteins myristoylated at the N terminus that regulate guanylate cyclases in photoreceptor cells and belong to the family of neuronal calcium sensors (NCS). Many NCS proteins display a recoverin-like "calcium-myristoyl switch" whereby the myristoyl group, buried inside the protein in the Ca(2+)-free state, becomes fully exposed upon Ca(2+) binding. Here we present a 2.0 A resolution crystal structure of myristoylated GCAP1 with Ca(2+) bound. The acyl group is buried inside Ca(2+)-bound GCAP1. This is in sharp contrast to Ca(2+)-bound recoverin, where the myristoyl group is solvent exposed. Furthermore, we provide direct evidence that the acyl group in GCAP1 remains buried in the Ca(2+)-free state and does not undergo switching. A pronounced kink in the C-terminal helix and the presence of the myristoyl group allow clustering of sequence elements crucial for GCAP1 activity.
Stephen
Ricardo
R
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80309, USA.
Bereta
Grzegorz
G
Golczak
Marcin
M
Palczewski
Krzysztof
K
Sousa
Marcelo Carlos
MC
D000818:Animals; D030161:Avian Proteins / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002645:Chickens; D018360:Crystallography, X-Ray; D051604:Guanylate Cyclase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009227:Myristic Acids / Q000737:chemistry; D011487:Protein Conformation
D030161:Avian Proteins; D051604:Guanylate Cyclase-Activating Proteins; D009227:Myristic Acids; D002118:Calcium