Recoverin is a neuronal calcium sensor involved in vision adaptation that reversibly associates with cellular membranes via its calcium-activated myristoyl switch. While experimental evidence shows that the myristoyl group significantly enhances membrane affinity of this protein, molecular details of the binding process are still under debate. Here, we present results of extensive molecular dynamics simulations of recoverin in the proximity of a phospholipid bilayer. We capture multiple events of spontaneous membrane insertion of the myristoyl moiety and confirm its critical role in the membrane binding. Moreover, we observe that the binding strongly depends on the conformation of the N-terminal domain. We propose that a suitable conformation of the N-terminal domain can be stabilized by the disordered C-terminal segment or by binding of the target enzyme, i.e., rhodopsin kinase. Finally, we find that the presence of negatively charged lipids in the bilayer stabilizes a physiologically functional orientation of the membrane-bound recoverin.

Department of Physics Tampere University of Technology P O Box 692 FI 33101 Tampere Finland

Faculty of Pharmacy University of Helsinki Viikinkaari 5E Helsinki 00014 Finland

Institute for Computational Physics University of Stuttgart Allmandring 3 Stuttgart 70569 Germany

Institute of Experimental Botany Czech Academy of Sciences Rozvojová 263 16502 Prague 6 Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nám 2 16610 Prague 6 Czech Republic

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