%0 Journal Article
%A Weiergräber, O. H.
%A Senin, I. I.
%A Philippov, P. P.
%A Granzin, J.
%A Koch, K.-W.
%T Impact of N-terminal myristoylation on the Ca2+-dependent conformational transition in recoverin
%J The journal of biological chemistry
%V 278
%@ 0021-9258
%C Bethesda, Md.
%I Soc.
%M PreJuSER-30298
%P 22972 - 22979
%D 2003
%Z Record converted from VDB: 12.11.2012
%X 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.
%K Amino Acid Substitution
%K Animals
%K Calcium: metabolism
%K Calcium-Binding Proteins: chemistry
%K Calcium-Binding Proteins: metabolism
%K Cattle
%K Crystallography, X-Ray
%K Eye Proteins
%K G-Protein-Coupled Receptor Kinase 1
%K Hippocalcin
%K Kinetics
%K Lipoproteins
%K Models, Molecular
%K Mutagenesis, Site-Directed
%K Myristic Acid: metabolism
%K Nerve Tissue Proteins
%K Protein Binding
%K Protein Conformation
%K Protein Kinases: metabolism
%K Protein Structure, Secondary
%K Recombinant Proteins: chemistry
%K Recombinant Proteins: metabolism
%K Recoverin
%K Rod Cell Outer Segment: metabolism
%K Tumor Markers, Biological: chemistry
%K Tumor Markers, Biological: metabolism
%K Calcium-Binding Proteins (NLM Chemicals)
%K Eye Proteins (NLM Chemicals)
%K Lipoproteins (NLM Chemicals)
%K Nerve Tissue Proteins (NLM Chemicals)
%K Recombinant Proteins (NLM Chemicals)
%K Tumor Markers, Biological (NLM Chemicals)
%K Recoverin (NLM Chemicals)
%K Hippocalcin (NLM Chemicals)
%K Myristic Acid (NLM Chemicals)
%K Calcium (NLM Chemicals)
%K Protein Kinases (NLM Chemicals)
%K G-Protein-Coupled Receptor Kinase 1 (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:12686556
%U <Go to ISI:>//WOS:000183503900104
%R 10.1074/jbc.M300447200
%U https://juser.fz-juelich.de/record/30298