ArticleThe Journal of biological chemistry2014
Identification of target binding site in photoreceptor guanylyl cyclase-activating protein 1 (GCAP1).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Clinical and Biochemical Characterization of Specific GUCY2D Alleles Associated With a Rare Form of Night Blindness.Investigative ophthalmology & visual science · 2025Article
- NMR Structure of Retinal Guanylate Cyclase Activating Protein 5 (GCAP5) with R22A Mutation That Abolishes Dimerization and Enhances Cyclase Activation.Biochemistry · 2024Article
- Article
- Structural basis of retinal membrane guanylate cyclase regulation by GCAP1 and RD3.Frontiers in molecular neuroscience · 2022Review
- NMR and EPR-DEER Structure of a Dimeric Guanylate Cyclase Activator Protein-5 from Zebrafish Photoreceptors.Biochemistry · 2021Article
- A NovelInternational journal of molecular sciences · 2021Article
- Regulation of retinal membrane guanylyl cyclase (RetGC) by negative calcium feedback and RD3 protein.Pflugers Archiv : European journal of physiology · 2021Review
- Structural Insights into Retinal Guanylate Cyclase Activator Proteins (GCAPs).International journal of molecular sciences · 2021Review
- Article
- Two clusters of surface-exposed amino acid residues enable high-affinity binding of retinal degeneration-3 (RD3) protein to retinal guanylyl cyclase.The Journal of biological chemistry · 2020Article
- Retinal guanylyl cyclase activation by calcium sensor proteins mediates photoreceptor degeneration in anThe Journal of biological chemistry · 2019Article
- A G86R mutation in the calcium-sensor protein GCAP1 alters regulation of retinal guanylyl cyclase and causes dominant cone-rod degeneration.The Journal of biological chemistry · 2019Article
- Functional characterization of a novelMolecular vision · 2019Article
- Guanylate cyclase-activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors.The Journal of biological chemistry · 2018Article
- Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina.Scientific reports · 2018Article
- Dimerization of Neuronal Calcium Sensor Proteins.Frontiers in molecular neuroscience · 2018Review
- Article
- Structural Characterization of Ferrous Ion Binding to Retinal Guanylate Cyclase Activator Protein 5 from Zebrafish Photoreceptors.Biochemistry · 2017Article
- The R838S Mutation in Retinal Guanylyl Cyclase 1 (RetGC1) Alters Calcium Sensitivity of cGMP Synthesis in the Retina and Causes Blindness in Transgenic Mice.The Journal of biological chemistry · 2016Article
- Allosteric communication pathways routed by CaScientific reports · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Retinal guanylyl cyclase (RetGC)-activating proteins (GCAPs) regulate visual photoresponse and trigger congenital retinal diseases in humans, but GCAP interaction with its target enzyme remains obscure. We mapped GCAP1 residues comprising the RetGC1 binding site by mutagenizing the entire surface of GCAP1 and testing the ability of each mutant to bind RetGC1 in a cell-based assay and to activate it in vitro. Mutations that most strongly affected the activation of RetGC1 localized to a distinct patch formed by the surface of non-metal-binding EF-hand 1, the loop and the exiting helix of EF-hand 2, and the entering helix of EF-hand 3. Mutations in the binding patch completely blocked activation of the cyclase without affecting Ca(2+) binding stoichiometry of GCAP1 or its tertiary fold. Exposed residues in the C-terminal portion of GCAP1, including EF-hand 4 and the helix connecting it with the N-terminal lobe of GCAP1, are not critical for activation of the cyclase. GCAP1 mutants that failed to activate RetGC1 in vitro were GFP-tagged and co-expressed in HEK293 cells with mOrange-tagged RetGC1 to test their direct binding in cyto. Most of the GCAP1 mutations introduced into the "binding patch" prevented co-localization with RetGC1, except for Met-26, Lys-85, and Trp-94. With these residues mutated, GCAP1 completely failed to stimulate cyclase activity but still bound RetGC1 and competed with the wild type GCAP1. Thus, RetGC1 activation by GCAP1 involves establishing a tight complex through the binding patch with an additional activation step involving Met-26, Lys-85, and Trp-94.
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