Journal Article

PreJuSER-30298

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impact of N-terminal myristoylation on the Ca2+-dependent conformational transition in recoverin

Weiergräber, O. H.FZJ* ; Senin, I. I. ; Philippov, P. P. ; Granzin, J.FZJ* ; Koch, K.-W.FZJ*

2003
Soc. Bethesda, Md.

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Please use a persistent id in citations: http://hdl.handle.net/2128/2643  doi:10.1074/jbc.M300447200

Abstract: Recoverin is a Ca2+-regulated signal transduction modulator found in vertebrate retina that has been shown to undergo dramatic conformational changes upon Ca2+ binding to its two functional EF-hand motifs. To elucidate the differential impact of the N-terminal myristoylation as well as occupation of the two Ca2+ binding sites on recoverin structure and function, we have investigated a non-myristoylated E85Q mutant exhibiting virtually no Ca2+ binding to EF-2. Crystal structures of the mutant protein as well as the non-myristoylated wild-type have been determined. Although the non-myristoylated E85Q mutant does not display any functional activity, its three-dimensional structure in the presence of Ca2+ resembles the myristoylated wild-type with two Ca2+ but is quite dissimilar from the myristoylated E85Q mutant. We conclude that the N-terminal myristoyl modification significantly stabilizes the conformation of the Ca2+-free protein (i.e. the T conformation) during the stepwise transition toward the fully Ca2+-occupied state. On the basis of these observations, a refined model for the role of the myristoyl group as an intrinsic allosteric modulator is proposed.

Keyword(s): Amino Acid Substitution (MeSH) ; Animals (MeSH) ; Calcium: metabolism (MeSH) ; Calcium-Binding Proteins: chemistry (MeSH) ; Calcium-Binding Proteins: metabolism (MeSH) ; Cattle (MeSH) ; Crystallography, X-Ray (MeSH) ; Eye Proteins (MeSH) ; G-Protein-Coupled Receptor Kinase 1 (MeSH) ; Hippocalcin (MeSH) ; Kinetics (MeSH) ; Lipoproteins (MeSH) ; Models, Molecular (MeSH) ; Mutagenesis, Site-Directed (MeSH) ; Myristic Acid: metabolism (MeSH) ; Nerve Tissue Proteins (MeSH) ; Protein Binding (MeSH) ; Protein Conformation (MeSH) ; Protein Kinases: metabolism (MeSH) ; Protein Structure, Secondary (MeSH) ; Recombinant Proteins: chemistry (MeSH) ; Recombinant Proteins: metabolism (MeSH) ; Recoverin (MeSH) ; Rod Cell Outer Segment: metabolism (MeSH) ; Tumor Markers, Biological: chemistry (MeSH) ; Tumor Markers, Biological: metabolism (MeSH) ; Calcium-Binding Proteins ; Eye Proteins ; Lipoproteins ; Nerve Tissue Proteins ; Recombinant Proteins ; Tumor Markers, Biological ; Recoverin ; Hippocalcin ; Myristic Acid ; Calcium ; Protein Kinases ; G-Protein-Coupled Receptor Kinase 1 ; J

Note: Record converted from VDB: 12.11.2012

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Contributing Institute(s):

1. Zelluläre Signalverarbeitung (IBI-1)
2. Biologische Strukturforschung (IBI-2)

Research Program(s):

1. Neurowissenschaften (L01)

Appears in the scientific report 2003

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Database coverage:

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