%0 Journal Article
%A Senin, I. I.
%A Vaganova, S. A.
%A Weiergräber, O. H.
%A Ergorov, N. S.
%A Philippov, P. P.
%A Koch, K.-W.
%T Functional restoration of the Ca2 -myristoyl switch in a recoverin mutant
%J Journal of molecular biology
%V 330
%@ 0022-2836
%C Amsterdam [u.a.]
%I Elsevier
%M PreJuSER-30299
%P 409 - 418
%D 2003
%Z Record converted from VDB: 12.11.2012
%X 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.
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000183824900020
%R 10.1016/S0022-2836(03)00581-3
%U https://juser.fz-juelich.de/record/30299