Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1

Structure. 2007 Nov;15(11):1392-402. doi: 10.1016/j.str.2007.09.013.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Avian Proteins / chemistry*
  • Avian Proteins / metabolism
  • Calcium / metabolism*
  • Chickens
  • Crystallography, X-Ray
  • Guanylate Cyclase-Activating Proteins / chemistry*
  • Guanylate Cyclase-Activating Proteins / metabolism
  • Humans
  • Models, Molecular
  • Myristic Acids / chemistry
  • Protein Conformation


  • Avian Proteins
  • Guanylate Cyclase-Activating Proteins
  • Myristic Acids
  • Calcium

Associated data

  • PDB/2R2I