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000030299 084__ $$2WoS$$aBiochemistry & Molecular Biology
000030299 1001_ $$0P:(DE-HGF)0$$aSenin, I. I.$$b0
000030299 245__ $$aFunctional restoration of the Ca2 -myristoyl switch in a recoverin mutant
000030299 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2003
000030299 300__ $$a409 - 418
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000030299 520__ $$aRecoverin is a neuronal calcium sensor protein that plays a crucial role in vertebrate phototransduction. It undergoes a Ca2+-myristoyl switch when Ca2+ binds to its two functional EF-hand motifs (EF-hands 2 and 3), each present in one of recoverin's two domains. Impairment of Ca2+-binding in recoverin leads to a disturbance of the Ca2+-myristoyl switch and loss of its regulatory properties, i.e. inhibiton of rhodopsin kinase. We have engineered recoverin mutants with either of the two functional EF-hands disabled, but with a functional Ca2+-binding site in EF-hand 4. While a defect in EF-hand 2 could not be rescued by the additional EF-hand 4, the impairment of EF-hand 3 was powerfully compensated by Ca2+-binding to EF-hand 4. For example, the myristoylated form of the latter mutant bound to membranes in a Ca2+-dependent way and was able to inhibit rhodopsin kinase in a way similar to that of the wild-type protein. Thus, for recoverin to undergo a Ca2+-myristoyl switch, it is necessary and sufficient to have either of the two EF-hands in the second domain in a functional state. On the basis of these results and inspection of published three-dimensional structures of recoverin, we propose a model highlighting the mutual interdependence of sterical configurations in EF-hands 3 and 4 of recoverin. (C) 2003 Elsevier Science Ltd. All rights reserved.
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000030299 65320 $$2Author$$acalcium sensor
000030299 65320 $$2Author$$aEF-hand protein
000030299 65320 $$2Author$$amyristoyl switch
000030299 65320 $$2Author$$arhodopsin kinase
000030299 65320 $$2Author$$aphototransduction
000030299 7001_ $$0P:(DE-HGF)0$$aVaganova, S. A.$$b1
000030299 7001_ $$0P:(DE-Juel1)131988$$aWeiergräber, O. H.$$b2$$uFZJ
000030299 7001_ $$0P:(DE-HGF)0$$aErgorov, N. S.$$b3
000030299 7001_ $$0P:(DE-HGF)0$$aPhilippov, P. P.$$b4
000030299 7001_ $$0P:(DE-Juel1)VDB789$$aKoch, K.-W.$$b5$$uFZJ
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000030299 8567_ $$uhttp://dx.doi.org/10.1016/S0022-2836(03)00581-3
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