Molecular mechanics of calcium-myristoyl switches

Nature. 1997 Sep 11;389(6647):198-202. doi: 10.1038/38310.


Many eukaryotic cellular and viral proteins have a covalently attached myristoyl group at the amino terminus. One such protein is recoverin, a calcium sensor in retinal rod cells, which controls the lifetime of photoexcited rhodopsin by inhibiting rhodopsin kinase. Recoverin has a relative molecular mass of 23,000 (M[r] 23K), and contains an amino-terminal myristoyl group (or related acyl group) and four EF hands. The binding of two Ca2+ ions to recoverin leads to its translocation from the cytosol to the disc membrane. In the Ca2+-free state, the myristoyl group is sequestered in a deep hydrophobic box, where it is clamped by multiple residues contributed by three of the EF hands. We have used nuclear magnetic resonance to show that Ca2+ induces the unclamping and extrusion of the myristoyl group, enabling it to interact with a lipid bilayer membrane. The transition is also accompanied by a 45-degree rotation of the amino-terminal domain relative to the carboxy-terminal domain, and many hydrophobic residues are exposed. The conservation of the myristoyl binding site and two swivels in recoverin homologues from yeast to humans indicates that calcium-myristoyl switches are ancient devices for controlling calcium-sensitive processes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / chemistry*
  • Calcium / metabolism
  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Crystallography, X-Ray
  • Escherichia coli
  • Eye Proteins*
  • Hippocalcin
  • Lipoproteins*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Myristic Acids / chemistry*
  • Myristic Acids / metabolism
  • Nerve Tissue Proteins*
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recoverin


  • Calcium-Binding Proteins
  • Eye Proteins
  • Lipoproteins
  • Myristic Acids
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • Recoverin
  • Hippocalcin
  • Calcium

Associated data

  • PDB/1JSA