ArticleThe Journal of biological chemistry2012
Calcium-myristoyl Tug is a new mechanism for intramolecular tuning of calcium sensitivity and target enzyme interaction for guanylyl cyclase-activating protein 1: dynamic connection between N-fatty acyl group and EF-hand controls calcium sensitivity.
Article in The Journal of biological chemistry, 2012. 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, 38 citations in OpenAlex.
- NMR Structure of Retinal Guanylate Cyclase Activating Protein 5 (GCAP5) with R22A Mutation That Abolishes Dimerization and Enhances Cyclase Activation.Biochemistry · 2024Article
- Calcium-sensor proteins but not bicarbonate ion activate retinal photoreceptor membrane guanylyl cyclase in photoreceptors.Frontiers in molecular neuroscience · 2024Article
- Chemical shift assignments of retinal guanylyl cyclase activating protein 5 (GCAP5) with a mutation (R22A) that abolishes dimerization and enhances cyclase activation.Biomolecular NMR assignments · 2023Article
- A fine balance of hydrophobic-electrostatic communication pathways in a pH-switching protein.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- NMR and EPR-DEER Structure of a Dimeric Guanylate Cyclase Activator Protein-5 from Zebrafish Photoreceptors.Biochemistry · 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
- A Novel Approach to Bacterial Expression and Purification of Myristoylated Forms of Neuronal Calcium Sensor Proteins.Biomolecules · 2020Article
- Constitutive Activation of Guanylate Cyclase by the G86R GCAP1 Variant Is Due to "Locking" Cation-π Interactions that Impair the Activator-to-Inhibitor Structural Transition.International journal of molecular sciences · 2020Article
- 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
- Evolutionary-Conserved Allosteric Properties of Three Neuronal Calcium Sensor Proteins.Frontiers in molecular neuroscience · 2019Article
- Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina.Scientific reports · 2018Article
- Functional Status of Neuronal Calcium Sensor-1 Is Modulated by Zinc Binding.Frontiers in molecular neuroscience · 2018Article
- Allosteric communication pathways routed by CaScientific reports · 2016Article
- Structure of Guanylyl Cyclase Activator Protein 1 (GCAP1) Mutant V77E in a Ca2+-free/Mg2+-bound Activator State.The Journal of biological chemistry · 2016Article
- Dimerization Domain of Retinal Membrane Guanylyl Cyclase 1 (RetGC1) Is an Essential Part of Guanylyl Cyclase-activating Protein (GCAP) Binding Interface.The Journal of biological chemistry · 2015Article
- Retina specific GCAPs in zebrafish acquire functional selectivity in Ca2+-sensing by myristoylation and Mg2+-binding.Scientific reports · 2015Article
- Evaluating the role of retinal membrane guanylyl cyclase 1 (RetGC1) domains in binding guanylyl cyclase-activating proteins (GCAPs).The Journal of biological chemistry · 2015Article
- Functional EF-hands in neuronal calcium sensor GCAP2 determine its phosphorylation state and subcellular distribution in vivo, and are essential for photoreceptor cell integrity.PLoS genetics · 2014Article
- Identification of target binding site in photoreceptor guanylyl cyclase-activating protein 1 (GCAP1).The Journal of biological chemistry · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Guanylyl cyclase-activating protein 1 (GCAP1), a myristoylated Ca(2+) sensor in vision, regulates retinal guanylyl cyclase (RetGC). We show that protein-myristoyl group interactions control Ca(2+) sensitivity, apparent affinity for RetGC, and maximal level of cyclase activation. Mutating residues near the myristoyl moiety affected the affinity of Ca(2+) binding to EF-hand 4. Inserting Phe residues in the cavity around the myristoyl group increased both the affinity of GCAP1 for RetGC and maximal activation of the cyclase. NMR spectra show that the myristoyl group in the L80F/L176F/V180F mutant remained sequestered inside GCAP1 in both Ca(2+)-bound and Mg(2+)-bound states. This mutant displayed much higher affinity for the cyclase but reduced Ca(2+) sensitivity of the cyclase regulation. The L176F substitution improved affinity of myristoylated and non-acylated GCAP1 for the cyclase but simultaneously reduced the affinity of Ca(2+) binding to EF-hand 4 and Ca(2+) sensitivity of the cyclase regulation by acylated GCAP1. The replacement of amino acids near both ends of the myristoyl moiety (Leu(80) and Val(180)) minimally affected regulatory properties of GCAP1. N-Lauryl- and N-myristoyl-GCAP1 activated RetGC in a similar fashion. Thus, protein interactions with the central region of the fatty acyl chain optimize GCAP1 binding to RetGC and maximize activation of the cyclase. We propose a dynamic connection (or "tug") between the fatty acyl group and EF-hand 4 via the C-terminal helix that attenuates the efficiency of RetGC activation in exchange for optimal Ca(2+) sensitivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.