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Open AccessArticle

Effects of Membrane and Biological Target on the Structural and Allosteric Properties of Recoverin: A Computational Approach

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Department of Neuroscience, Biomedicine and Movement Sciences, Section of Biological Chemistry, University of Verona, 37134 Verona, Italy
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Department of Physics, University of Trento, 38123 Trento, Italy
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Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56026 Pisa, Italy
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Trento Institute for Fundamental Physics and Applications (INFN-TIFPA), Via Sommarive 14, Povo, 38123 Trento, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5009; https://doi.org/10.3390/ijms20205009
Received: 20 September 2019 / Revised: 1 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Lipid-Protein and Protein-Protein Interactions in Membranes)
Recoverin (Rec) is a prototypical calcium sensor protein primarily expressed in the vertebrate retina. The binding of two Ca2+ ions to the functional EF-hand motifs induces the extrusion of a myristoyl group that increases the affinity of Rec for the membrane and leads to the formation of a complex with rhodopsin kinase (GRK1). Here, unbiased all-atom molecular dynamics simulations were performed to monitor the spontaneous insertion of the myristoyl group into a model multicomponent biological membrane for both isolated Rec and for its complex with a peptide from the GRK1 target. It was found that the functional membrane anchoring of the myristoyl group is triggered by persistent electrostatic protein-membrane interactions. In particular, salt bridges between Arg43, Arg46 and polar heads of phosphatidylserine lipids are necessary to enhance the myristoyl hydrophobic packing in the Rec-GRK1 assembly. The long-distance communication between Ca2+-binding EF-hands and residues at the interface with GRK1 is significantly influenced by the presence of the membrane, which leads to dramatic changes in the connectivity of amino acids mediating the highest number of persistent interactions (hubs). In conclusion, specific membrane composition and allosteric interactions are both necessary for the correct assembly and dynamics of functional Rec-GRK1 complex. View Full-Text
Keywords: recoverin; myristoyl switch; molecular dynamics; phototransduction; rhodopsin kinase; protein structure networks recoverin; myristoyl switch; molecular dynamics; phototransduction; rhodopsin kinase; protein structure networks
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Borsatto, A.; Marino, V.; Abrusci, G.; Lattanzi, G.; Dell’Orco, D. Effects of Membrane and Biological Target on the Structural and Allosteric Properties of Recoverin: A Computational Approach. Int. J. Mol. Sci. 2019, 20, 5009.

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