This title appears in the Scientific Report : 2003 

Functional restoration of the Ca2 -myristoyl switch in a recoverin mutant
Senin, I. I.
Vaganova, S. A. / Weiergräber, O. H. / Ergorov, N. S. / Philippov, P. P. / Koch, K.-W.
Zelluläre Signalverarbeitung; IBI-1
Biologische Strukturforschung; IBI-2
Journal of molecular biology, 330 (2003) S. 409 - 418
Amsterdam [u.a.] Elsevier 2003
409 - 418
Journal Article
Journal of Molecular Biology 330
Please use the identifier: in citations.
Recoverin 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.