Abstract
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.
Highlights
Intracellular calcium ion (Ca2+) is a second messenger in the brain and retina that modulates sensory signal transduction processes (Berridge et al, 2000; Augustine et al, 2003)
neuronal calcium sensor (NCS) homologs are expressed in the brain and spinal cord, such as neurocalcin (Hidaka and Okazaki, 1993), frequenin (NCS-1; Pongs et al, 1993; McFerran et al, 1998), visinin-like proteins (VILIPs; Bernstein et al, 1999; Braunewell and Klein-Szanto, 2009) and hippocalcin (Kobayashi et al, 1992, 1993; Tzingounis et al, 2007)
The fourth EF-hand sequence is variable, and Ca2+ is able to bind to EF4 in neurocalcin-δ (Ladant, 1995) and GCAPs (Peshenko and Dizhoor, 2007; Stephen et al, 2007) but Ca2+ does not bind to EF4 in recoverin (Ames et al, 1995) and VILIPs (Cox et al, 1994; Li et al, 2011)
Summary
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. VILIP1 binds to membrane targets that modulate neuronal secretion. 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. Reviewed by: Eugene Anatolievich Permyakov, Institute for Biological Instrumentation (RAS), Russia Rameshwar K.
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