Dimerization of Neuronal Calcium Sensor Proteins

Neuronal calcium sensor (NCS) proteins are EF-hand containing Ca2+ binding proteins that regulate sensory signal transduction. Many NCS proteins (recoverin, GCAPs, neurocalcin and visinin-like protein 1 (VILIP1)) form functional dimers under physiological conditions. The dimeric NCS proteins have similar amino acid sequences (50% homology) but each bind to and regulate very different physiological targets. Retinal recoverin binds to rhodopsin kinase and promotes Ca2+-dependent desensitization of light-excited rhodopsin during visual phototransduction. The guanylyl cyclase activating proteins (GCAP1-5) each bind and activate retinal guanylyl cyclases (RetGCs) in light-adapted photoreceptors. VILIP1 binds to membrane targets that modulate neuronal secretion. Here, I review atomic-level structures of dimeric forms of recoverin, GCAPs and VILIP1. The distinct dimeric structures in each case suggest that NCS dimerization may play a role in modulating specific target recognition. The dimerization of recoverin and VILIP1 is Ca2+-dependent and enhances their membrane-targeting Ca2+-myristoyl switch function. The dimerization of GCAP1 and GCAP2 facilitate their binding to dimeric RetGCs and may allosterically control the Ca2+-dependent activation of RetGCs