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Journal article
Ca2+ and Mg2+ binding properties of GCAP-1 - Evidence that Mg2+-bound form is the physiological activator of photoreceptor guanylyl cyclase
The Journal of biological chemistry, v 281(33), pp 23830-23841
18 Aug 2006
PMID: 16793776
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Guanylyl cyclase-activating protein 1 (GCAP-1) is an EF-hand protein that activates retinal guanylyl cyclase ( RetGC) in photoreceptors at low free Ca2+ in the light and inhibits it in the dark when Ca2+ concentrations rise. We present the first direct evidence that Mg2+-bound form of GCAP-1, not its cation-free form, is the true activator of RetGC-1 under physiological conditions. Of four EF-hand structures in GCAP-1, three bound Ca2+ ions and could exchange Ca2+ for Mg2+. At concentrations of free Ca2+ and Mg2+ typical for the light-adapted photoreceptors, all three metal-binding EF-hands were predominantly occupied by Mg-2, and the presence of bound Mg2+ in GCAP-1 was essential for its ability to stimulate RetGC-1. In the Mg2+- bound form of GCAP-1 all three Trp residues became more exposed to the polar environment compared with its apo form. The replacement of Mg2+ by Ca2+ in the EF-hands 2 and 3 further exposed Trp-21 to the solution in a non-metal-binding EF-hand domain 1 that interacts with RetGC. Contrary to that, replacement of Mg2+ by Ca2+ in the EF-hand 4 moved Trp-94 in the entering alpha-helix of the EF-hand 3 back to the non-polar environment. Our results demonstrate that Mg2+ regulates GCAP-1 not only by adjusting its Ca2+ sensitivity to the physiological conditions in photoreceptors but also by creating the conformation required for RetGC stimulation.
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Details
- Title
- Ca2+ and Mg2+ binding properties of GCAP-1 - Evidence that Mg2+-bound form is the physiological activator of photoreceptor guanylyl cyclase
- Creators
- Igor V. Peshenko - Salus UniversityAlexander M. Dizhoor - Salus University
- Publication Details
- The Journal of biological chemistry, v 281(33), pp 23830-23841
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 12
- 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; R01 EY011522-11 / NEI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000239702900059
- Scopus ID
- 2-s2.0-33747709435
- Other Identifier
- 991022035114904721
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- Web of Science research areas
- Biochemistry & Molecular Biology