This title appears in the Scientific Report :
2003
Please use the identifier:
http://dx.doi.org/10.1016/S0022-2836(03)00581-3 in citations.
Functional restoration of the Ca2 -myristoyl switch in a recoverin mutant
Functional restoration of the Ca2 -myristoyl switch in a recoverin mutant
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 r...
Saved in:
Personal Name(s): | Senin, I. I. |
---|---|
Vaganova, S. A. / Weiergräber, O. H. / Ergorov, N. S. / Philippov, P. P. / Koch, K.-W. | |
Contributing Institute: |
Zelluläre Signalverarbeitung; IBI-1 Biologische Strukturforschung; IBI-2 |
Published in: | Journal of molecular biology, 330 (2003) S. 409 - 418 |
Imprint: |
Amsterdam [u.a.]
Elsevier
2003
|
Physical Description: |
409 - 418 |
DOI: |
10.1016/S0022-2836(03)00581-3 |
Document Type: |
Journal Article |
Research Program: |
Neurowissenschaften |
Series Title: |
Journal of Molecular Biology
330 |
Subject (ZB): | |
Publikationsportal JuSER |
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. |