TY  - JOUR
AU  - Weiergräber, O. H.
AU  - Senin, I. I.
AU  - Philippov, P. P.
AU  - Granzin, J.
AU  - Koch, K.-W.
TI  - Impact of N-terminal myristoylation on the Ca2+-dependent conformational transition in recoverin
JO  - The journal of biological chemistry
VL  - 278
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - PreJuSER-30298
SP  - 22972 - 22979
PY  - 2003
N1  - Record converted from VDB: 12.11.2012
AB  - 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.
KW  - Amino Acid Substitution
KW  - Animals
KW  - Calcium: metabolism
KW  - Calcium-Binding Proteins: chemistry
KW  - Calcium-Binding Proteins: metabolism
KW  - Cattle
KW  - Crystallography, X-Ray
KW  - Eye Proteins
KW  - G-Protein-Coupled Receptor Kinase 1
KW  - Hippocalcin
KW  - Kinetics
KW  - Lipoproteins
KW  - Models, Molecular
KW  - Mutagenesis, Site-Directed
KW  - Myristic Acid: metabolism
KW  - Nerve Tissue Proteins
KW  - Protein Binding
KW  - Protein Conformation
KW  - Protein Kinases: metabolism
KW  - Protein Structure, Secondary
KW  - Recombinant Proteins: chemistry
KW  - Recombinant Proteins: metabolism
KW  - Recoverin
KW  - Rod Cell Outer Segment: metabolism
KW  - Tumor Markers, Biological: chemistry
KW  - Tumor Markers, Biological: metabolism
KW  - Calcium-Binding Proteins (NLM Chemicals)
KW  - Eye Proteins (NLM Chemicals)
KW  - Lipoproteins (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - Tumor Markers, Biological (NLM Chemicals)
KW  - Recoverin (NLM Chemicals)
KW  - Hippocalcin (NLM Chemicals)
KW  - Myristic Acid (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
KW  - Protein Kinases (NLM Chemicals)
KW  - G-Protein-Coupled Receptor Kinase 1 (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:12686556
UR  - <Go to ISI:>//WOS:000183503900104
DO  - DOI:10.1074/jbc.M300447200
UR  - https://juser.fz-juelich.de/record/30298
ER  -