Download MendeleyMolecular mechanics of calcium-myristoyl switches.
Ames, J.B., Ishima, R., Tanaka, T., Gordon, J.I., Stryer, L., Ikura, M.(1997) Nature 389: 198-202
- PubMed: 9296500
- DOI: https://doi.org/10.1038/38310
- Primary Citation of Related Structures:
1JSA - PubMed Abstract:
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.
Organizational Affiliation:
Department of Neurobiology, Stanford University School of Medicine, California 94305, USA.
