Tuning of a neuronal calcium sensor.
Recoverin is a Ca(2+)-regulated signal transduction modulator expressed in the vertebrate retina that has been implicated in visual adaptation. An intriguing feature of recoverin is a cluster of charged residues at its C terminus, the functional significance of which is largely unclear. To elucidate the impact of this segment on recoverin structure and function, we have investigated a mutant lacking the C-terminal 12 amino acids. Whereas in myristoylated recoverin the truncation causes an overall decrease in Ca(2+) sensitivity, results for the non-myristoylated mutant indicate that the truncation primarily affects the high affinity EF-hand 3. The three-dimensional structure of the mutant has been determined by x-ray crystallography. In addition to significant changes in average coordinates compared with wild-type recoverin, the structure provides strong indication of increased conformational flexibility, particularly in the C-terminal domain. Based on these observations, we propose a novel role of the C-terminal segment of recoverin as an internal modulator of Ca(2+) sensitivity.
Weiergräber
Oliver H
OH
Institut für Biologische Informationsverarbeitung (IBI-2, Biologische Strukturforschung), Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany.
Senin
Ivan I
II
Zernii
Eugene Yu
EY
Churumova
Valeriya A
VA
Kovaleva
Nadezhda A
NA
Nazipova
Aliya A
AA
Permyakov
Sergei E
SE
Permyakov
Eugene A
EA
Philippov
Pavel P
PP
Granzin
Joachim
J
Koch
Karl-Wilhelm
KW
D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling / Q000502:physiology*; D002417:Cattle; D018360:Crystallography, X-Ray; D017931:DNA Primers / Q000235:genetics; D066298:In Vitro Techniques; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051603:Recoverin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism*; D017384:Sequence Deletion; D020349:Surface Plasmon Resonance
D017931:DNA Primers; C067574:RCV1 protein, Bos taurus; D011994:Recombinant Proteins; D051603:Recoverin