Modulation of guanylate cyclase activating protein 1 (Gcap1) dimeric assembly by ca2+ or mg2+: Hints to understand protein activity
Academic Article
Publication Date:
2020
abstract:
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
Iris type:
01.01 Articolo in rivista
Keywords:
calcium ion; guanylate cyclase activating protein 1; guanylate cyclase activator; magnesium ion; recombinant human guanylate cyclase activating protein 1; unclassified drug; calcium; guanylate cyclase activator; GUCA1A protein; human; magnesium; amino acid sequence; Article; binding affinity; circular dichroism; computer model; computer simulation; conformational transition; controlled study; crystal structure; dimerization; Escherichia coli; fluorescence; molecular docking; molecular dynamics; nonhuman; photon correlation spectroscopy; polyacrylamide gel electrophoresis; protein binding; protein denaturation; protein expression; protein protein interaction; protein purification; protein stability; protein structure; size exclusion chromatography; chemistry; human; metabolism; molecular dynamics; protein multimerization; Calcium; Guanylate Cyclase-Activating Proteins; Humans; Magnesium; Molecular Dynamics Simulation; Pro
List of contributors:
Boni, Francesco; MILANI DE MAYO DE MARI, Mario; Mastrangelo, Eloise
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