Recoverin, a calcium-activated myristoyl switch

Function

Recoverin is a 23 kD protein that regulates recovery of the eye from exposure to light, and the adaptation to background light. Recoverin controls the lifetime of photoactivated rhodopsin. Recoverin in turn is regulated by calcium ions, which cause recoverin molecules to associate with the disc membranes which fill the photosensitive portion of the rod cells in the eye, rather than diffusing freely in the cytosol.

Myristoyl Switch and Calcium

(Initial colors: Hydrophobic, Polar) has a (14-carbon saturated fatty acid, or a similar acyl moiety) covalently linked via an amide bond to its N-terminal glycine. In the absence of calcium, the in the N-terminal protein domain, surrounded on all sides by alpha helices that form a hydrophobic pocket. The binding of to each recoverin molecule induces a that extrudes the myristoyl and exposes some hydrophobic amino acids on the surface. This enables the molecule to bind to the lipid bilayers of the disc membranes. ^[1] emphasizes that two parts of the molecule rotate relative to each other while retaining their local fold.

The two calcium ions each bind to an EF hand motif, one in the C-terminal domain, and one in the N-terminal domain. Recoverin actually contains four EF hand motifs, but two of them are unable to bind calcium due to variations in sequence.

Recoverin, which has been described as a calcium-myristoyl switch, is a member of a large family of sequence-similar proteins found from yeast through invertebrates and mammals. Those found in the nervous system are suspected to "participate in membrane-associated signal transduction processes by coupling G-protein receptors to calcium cascades" (Tanaka et al., 1995^[2]).

3D Structure

Recoverin was the first member of the calcium-myristoyl switch family family whose 3D structure was determined. The structure of the calcium-free form was determined by solution NMR in 1995^[2]. Determination of the calcium-bound, hydrophobic form by solution NMR required modification of the myristoyl: carbon in the 13th position was replaced with oxygen (Ames et al., 1997^[3]). The 13-oxa myristoyl analog recoverin retains a functional calcium-myristoyl switch, and the calcium-bound conformation is very similar to the natural form (by heteronuclear single quantum coherence spectra).

The Morphs provided here illustrate the structural relationships between the calcium-free, water-soluble conformation, and the calcium-bound, hydrophobic conformation.

Technical Notes

Both 1iku and 1jsa are ensembles of NMR models. The morph is a linear interpolation morph between model 7 and model 9, respectively. Only the alpha carbon atoms of the protein are present in the morph PDB file. For the space-filled model 7 of 1iku, hydrogen atoms were deleted except for those in the myristoyl adduct. The alternate morph preserving rigid domains was created using the Storymorph Jmol scripts.