Phosphorylation of the minimal inhibitory region at the C-terminus of caldesmon alters its structural and actin binding properties.
Caldesmon is an inhibitory protein believed to be involved in the regulation of thin filament activity in smooth muscles and is a major cytoplasmic substrate for MAP kinase. NMR spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon MAP kinase phosphorylation of Ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to F-actin. The structural basis for the altered interaction is identified from the observation that phosphorylation destabilises a turn segment linking the two actin binding sites and thereby results in the randomisation of their relative disposition. This modulatory influence of Ser-759 phosphorylation is not merely a function of the bulkiness of the covalent modification since the stability of the turn region is observed to be sensitive to the ionisation state of the phosphate group. The data are discussed in the context of the inhibitory association of the C-terminal domain of caldesmon with F-actin.
Patchell
Valerie B
VB
School of Medicine, University of Birmingham, Birmingham B15 2TT, UK.
Vorotnikov
Alexander V
AV
Gao
Yuan
Y
Low
Douglas G
DG
Evans
James S
JS
Fattoum
Abdellatif
A
El-Mezgueldi
Mohammed
M
Marston
Steven B
SB
Levine
Barry A
BA
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001665:Binding Sites; D002148:Calmodulin-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D009218:Myosins / Q000037:antagonists & inhibitors; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011487:Protein Conformation; D012694:Serine / Q000737:chemistry
D000199:Actins; D002148:Calmodulin-Binding Proteins; D010455:Peptides; D012694:Serine; D009218:Myosins