TY - JOUR
AU - Senin, I. I.
AU - Vaganova, S. A.
AU - Weiergräber, O. H.
AU - Ergorov, N. S.
AU - Philippov, P. P.
AU - Koch, K.-W.
TI - Functional restoration of the Ca2 -myristoyl switch in a recoverin mutant
JO - Journal of molecular biology
VL - 330
SN - 0022-2836
CY - Amsterdam [u.a.]
PB - Elsevier
M1 - PreJuSER-30299
SP - 409 - 418
PY - 2003
N1 - Record converted from VDB: 12.11.2012
AB - 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.
KW - J (WoSType)
LB - PUB:(DE-HGF)16
UR - <Go to ISI:>//WOS:000183824900020
DO - DOI:10.1016/S0022-2836(03)00581-3
UR - https://juser.fz-juelich.de/record/30299
ER -