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Sci. Signal., 26 January 2010
Vol. 3, Issue 106, p. ra6
[DOI: 10.1126/scisignal.2000552]

RESEARCH ARTICLES

Molecular Basis of the Death-Associated Protein Kinase–Calcium/Calmodulin Regulator Complex

Iñaki de Diego*, Jochen Kuper*{dagger}, Neda Bakalova, Petri Kursula{ddagger}, and Matthias Wilmanns§

European Molecular Biology Laboratory–Hamburg, Notkestrasse 85, D-22603 Hamburg, Germany.

* These authors contributed equally to this work.

{dagger} Present address: Rudolf Virchow Center for Biomedical Research, Versbacherstrasse 9, D-97078 Würzburg, Germany.

{ddagger} Present address: Center for Structural Systems Biology–Helmholtz Center for Infection Research, Deutsches Elektronen Synchrotron, Notkestrasse 85, D-22607 Hamburg, Germany.

Abstract: 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.

§ To whom correspondence should be addressed. E-mail: wilmanns{at}embl-hamburg.de

Citation: I. de Diego, J. Kuper, N. Bakalova, P. Kursula, M. Wilmanns, Molecular Basis of the Death-Associated Protein Kinase–Calcium/Calmodulin Regulator Complex. Sci. Signal. 3, ra6 (2010).

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