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Modulation of Guanylate Cyclase Activating Protein 1 (GCAP1) Dimeric Assembly by Ca2+ or Mg2+: Hints to Understand Protein Activity

1
CNR-IBF, Istituto di Biofisica, Via Celoria 26, I-20133 Milan, Italy
2
Dipartimento di Bioscienze, Università di Milano, Via Celoria 26, I-20133 Milan, Italy
3
Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Chimica Biologica, Università di Verona, I-37134 Verona, Italy
4
Dipartimento di Scienze per gli Alimenti, la Nutrizione e l’Ambiente, Università degli Studi di Milano, Via Celoria 2, I-20133 Milan, Italy
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(10), 1408; https://doi.org/10.3390/biom10101408
Received: 17 September 2020 / Revised: 30 September 2020 / Accepted: 1 October 2020 / Published: 5 October 2020
(This article belongs to the Special Issue Metal Binding Proteins 2020)
The guanylyl cyclase-activating protein 1, GCAP1, activates or inhibits retinal guanylyl cyclase (retGC) depending on cellular Ca2+ concentrations. Several point mutations of GCAP1 have been associated with impaired calcium sensitivity that eventually triggers progressive retinal degeneration. In this work, we demonstrate that the recombinant human protein presents a highly dynamic monomer-dimer equilibrium, whose dissociation constant is influenced by salt concentration and, more importantly, by protein binding to Ca2+ or Mg2+. Based on small-angle X-ray scattering data, protein-protein docking, and molecular dynamics simulations we propose two novel three-dimensional models of Ca2+-bound GCAP1 dimer. The different propensity of human GCAP1 to dimerize suggests structural differences induced by cation binding potentially involved in the regulation of retGC activity. View Full-Text
Keywords: quaternary assembly; calcium-binding proteins; EF-hand; protein-protein interaction; small-angle X-ray scattering; molecular dynamics simulations; protein modeling; protein dynamics; size exclusion chromatography; multi-angle light scattering quaternary assembly; calcium-binding proteins; EF-hand; protein-protein interaction; small-angle X-ray scattering; molecular dynamics simulations; protein modeling; protein dynamics; size exclusion chromatography; multi-angle light scattering
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MDPI and ACS Style

Bonì, F.; Marino, V.; Bidoia, C.; Mastrangelo, E.; Barbiroli, A.; Dell’Orco, D.; Milani, M. Modulation of Guanylate Cyclase Activating Protein 1 (GCAP1) Dimeric Assembly by Ca2+ or Mg2+: Hints to Understand Protein Activity. Biomolecules 2020, 10, 1408. https://doi.org/10.3390/biom10101408

AMA Style

Bonì F, Marino V, Bidoia C, Mastrangelo E, Barbiroli A, Dell’Orco D, Milani M. Modulation of Guanylate Cyclase Activating Protein 1 (GCAP1) Dimeric Assembly by Ca2+ or Mg2+: Hints to Understand Protein Activity. Biomolecules. 2020; 10(10):1408. https://doi.org/10.3390/biom10101408

Chicago/Turabian Style

Bonì, Francesco, Valerio Marino, Carlo Bidoia, Eloise Mastrangelo, Alberto Barbiroli, Daniele Dell’Orco, and Mario Milani. 2020. "Modulation of Guanylate Cyclase Activating Protein 1 (GCAP1) Dimeric Assembly by Ca2+ or Mg2+: Hints to Understand Protein Activity" Biomolecules 10, no. 10: 1408. https://doi.org/10.3390/biom10101408

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