Journal
OPEN BIOLOGY
Volume 11, Issue 1, Pages -Publisher
ROYAL SOC
DOI: 10.1098/rsob.200346
Keywords
conformational selection; myristoyl switch; neuronal calcium sensor; phototransduction; rhodopsin kinase
Categories
Funding
- Italian Ministry of Research and Education
- DFG [KO948/15-1]
- Consorzio Interuniversitario Biotecnologie
- Erasmus+ grant
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This study investigates the mechanism by which the calcium-sensor protein recoverin regulates the activity of rhodopsin kinase in photoreceptors. The presence of both GRK1 and membrane is crucial for the physiological response to changes in intracellular calcium levels, driving the structural transitions of recoverin via a conformational selection mechanism. These findings may have implications for other sensory transduction systems involving protein complexes and biological membranes.
The prototypical Ca2+-sensor protein recoverin (Rec) is thought to regulate the activity of rhodopsin kinase (GRK1) in photoreceptors by switching from a relaxed (R) disc membrane-bound conformation in the dark to a more compact, cytosol-diffusing tense (T) conformation upon cell illumination. However, the apparent affinity for Ca2+ of its physiologically relevant form (myristoylated recoverin) is almost two orders of magnitude too low to support this mechanism in vivo. In this work, we compared the individual and synergistic roles of the myristic moiety, the GRK1 target and the disc membrane in modulating the calcium sensitivity of Rec. We show that the sole presence of the target or the disc membrane alone are not sufficient to achieve a physiological response to changes in intracellular [Ca2+]. Instead, the simultaneous presence of GRK1 and membrane allows the T to R transition to occur in a physiological range of [Ca2+] with high cooperativity via a conformational selection mechanism that drives the structural transitions of Rec in the presence of multiple ligands. Our conclusions may apply to other sensory transduction systems involving protein complexes and biological membranes.
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