posted on 2018-03-14, 00:00authored byŠtěpán Timr, Jan Kadlec, Pavel Srb, O. H. Samuli Ollila, Pavel Jungwirth
The
detailed functional mechanism of recoverin, which acts as a
myristoyl switch at the rod outer-segment disk membrane, is elucidated
by direct and replica-exchange molecular dynamics. In accord with
NMR structural evidence and calcium binding assays, simulations point
to the key role of enhanced calcium binding to the EF3 loop of the
semiopen state of recoverin as compared to the closed state. This
2–4-order decrease in calcium dissociation constant stabilizes
the semiopen state in response to the increase of cytosolic calcium
concentration in the vicinity of recoverin. A second calcium ion then
binds to the EF2 loop and, consequently, the structure of the protein
changes from the semiopen to the open state. The latter has the myristoyl
chain extruded to the cytosol, ready to act as a membrane anchor of
recoverin.