Molecular basis of the death-associated protein kinase-calcium/calmodulin regulator complex

Death-associated protein kinase (DAPK) provides a model for calcium-bound calmodulin (CaM)-dependent protein kinases (CaMKs). Here, we report the crystal structure of the binary DAPK-CaM complex, using a construct that includes the DAPK catalytic domain and adjacent autoregulatory domain. When DAPK...

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Bibliographic Details
Published in:Science signaling 2010-01, Vol.3 (106), p.ra6-ra6
Main Authors: de Diego, Iñaki, Kuper, Jochen, Bakalova, Neda, Kursula, Petri, Wilmanns, Matthias
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Apoptosis Regulatory Proteins - chemistry
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Calcium - chemistry
Calcium - metabolism
Calcium-Calmodulin-Dependent Protein Kinases - chemistry
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Calmodulin - chemistry
Calmodulin - metabolism
Catalysis
Catalytic Domain
Crystallography, X-Ray
Death-Associated Protein Kinases
Electrophoresis, Polyacrylamide Gel
Humans
Models, Molecular
Molecular Sequence Data
Phosphorylation
Protein Binding
Protein Conformation
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Homology, Amino Acid
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Summary:Death-associated protein kinase (DAPK) provides a model for calcium-bound calmodulin (CaM)-dependent protein kinases (CaMKs). Here, we report the crystal structure of the binary DAPK-CaM complex, using a construct that includes the DAPK catalytic domain and adjacent autoregulatory domain. When DAPK was in a complex with CaM, the DAPK autoregulatory domain formed a long seven-turn helix. This DAPK-CaM module interacted with the DAPK catalytic domain through two separate domain-domain interfaces, which involved the upper and the lower lobe of the catalytic domain. When bound to DAPK, CaM adopted an extended conformation, which was different from that in CaM-CaMK peptide complexes. Complementary biochemical analysis showed that the ability of DAPK to bind CaM correlated with its catalytic activity. Because many features of CaM binding are conserved in other CaMKs, our findings likely provide a generally applicable model for regulation of CaMK activity.
ISSN:1945-0877
1937-9145
DOI:10.1126/scisignal.2000552