Molecular mechanics of calcium-myristoyl switches.
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.
Ames
J B
JB
Department of Neurobiology, Stanford University School of Medicine, California 94305, USA.
Ishima
R
R
Tanaka
T
T
Gordon
J I
JI
Stryer
L
L
Ikura
M
M
D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D005136:Eye Proteins; D051597:Hippocalcin; D008074:Lipoproteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009227:Myristic Acids / Q000737:chemistry* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D051603:Recoverin
D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D008074:Lipoproteins; D009227:Myristic Acids; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D051603:Recoverin; D051597:Hippocalcin; D002118:Calcium