Journal article
Interaction of GCAP1 with retinal guanylyl cyclase and calcium: sensitivity to fatty acylation
Frontiers in molecular neuroscience, v 5(2012), 19
01 Jan 2012
PMID: 22371697
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Guanylyl cyclase activating proteins (GCAPs) are calcium/magnesium binding proteins within neuronal calcium sensor proteins group (NCS) of the FE-hand proteins superfamily. GCAPs activate retinal guanylyl cyclase (RetGC) in vertebrate photoreceptors in response to light-dependent fall of the intracellular free Ca2+ concentrations. GCAPs consist of four FE hand domains and contain N-terminal fatty acylated glycine, which in GCAP1 is required for the normal activation of RetGC. We analyzed the effects of a substitution prohibiting N-myristoylation (Gly2 -> Ala) on the ability of the recombinant GCAP1 to co-localize with its target enzyme when heterologously expressed in HEK293 cells. We also compared Ca2+ binding and RetGC-activating properties of the purified non-acylated G2A mutant and C14:0 acylated GCAP1 in vitro. The G2A GCAP1 expressed with a C-terminal GEE tag was able to co-localize with the cyclase, albeit less efficiently than the wild type, but much less effectively stimulated cyclase activity in vitro. Ca2+ binding isotherm of the G2A GCAP1 was slightly shifted toward higher free Ca2+ concentrations and so was Ca2+ sensitivity of RetGC reconstituted with the G2A mutant. At the same time, myristoylation had little effect on the high-affinity Ca2+-binding in the FE-hand proximal to the myristoyl residue in three-dimensional GCAP1 structure. These data indicate that the N-terminal fatty acyl group may alter the activity of EE-hands in the distal portion of the GCAP1 molecule via presently unknown intrarnolecular mechanism.
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Details
- Title
- Interaction of GCAP1 with retinal guanylyl cyclase and calcium: sensitivity to fatty acylation
- Creators
- Igor V. Peshenko - Salus UniversityElena V. Olshevskaya - Salus UniversityAlexander M. Dizhoor - Salus University
- Publication Details
- Frontiers in molecular neuroscience, v 5(2012), 19
- Publisher
- Frontiers Media Sa
- Number of pages
- 8
- Grant note
- R01EY011522 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) EY11522 / NIH from NEI
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000209202600019
- Scopus ID
- 2-s2.0-84857314368
- Other Identifier
- 991022035116204721
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- Web of Science research areas
- Neurosciences