Membrane Binding of Recoverin : From Mechanistic Understanding to Biological Functionality
| Autor: | Roman Pleskot, Štěpán Timr, Miriam Kohagen, Pavel Jungwirth, Aniket Magarkar, Jan Kadlec |
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| Přispěvatelé: | University of Helsinki, Faculty of Pharmacy |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
General Chemical Engineering 116 Chemical sciences 01 natural sciences MYRISTOYLATED PROTEINS VALIDATION lcsh:Chemistry 03 medical and health sciences Molecular dynamics Recoverin 0103 physical sciences GUI Moiety SWITCH Lipid bilayer LIPID-BILAYERS Myristoylation 010304 chemical physics biology Chemistry Bilayer General Chemistry SIMULATIONS 3. Good health Rhodopsin kinase 030104 developmental biology Membrane Biochemistry lcsh:QD1-999 MOLECULAR-DYNAMICS 317 Pharmacy Biophysics biology.protein FORCE-FIELD lipids (amino acids peptides and proteins) NEURONAL CALCIUM-SENSOR CHARMM Research Article |
| Zdroj: | ACS Central Science, Vol 3, Iss 8, Pp 868-874 (2017) ACS Central Science |
| Popis: | 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. Molecular dynamics simulations provide atomistic insights into the reversible membrane binding of recoverin, demonstrating the key role of the myristoyl moiety for the membrane association. |
| Databáze: | OpenAIRE |
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