2A2A

High-resolution crystallographic analysis of the autoinhibited conformation of a human death-associated protein kinase

Summary for 2A2A

• Entry DOI: 10.2210/pdb2a2a/pdb
• Related: 2A27
• Descriptor: Death-associated protein kinase 2, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: protein kinase, autoinhibition, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9UIK4
• Total number of polymer chains: 4
• Total formula weight: 149849.58

Authors

Kursula, P.,Wilmanns, M. (deposition date: 2005-06-22, release date: 2006-10-17, Last modification date: 2023-10-25)

Primary citation

Simon, B.,Huart, A.S.,Temmerman, K.,Vahokoski, J.,Mertens, H.D.,Komadina, D.,Hoffmann, J.E.,Yumerefendi, H.,Svergun, D.I.,Kursula, P.,Schultz, C.,McCarthy, A.A.,Hart, D.J.,Wilmanns, M.
Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites
Structure, 2016

PubMed Abstract: The regulation of many protein kinases by binding to calcium/calmodulin connects two principal mechanisms in signaling processes: protein phosphorylation and responses to dose- and time-dependent calcium signals. We used the calcium/calmodulin-dependent members of the death-associated protein kinase (DAPK) family to investigate the role of a basic DAPK signature loop near the kinase active site. In DAPK2, this loop comprises a novel dimerization-regulated calcium/calmodulin-binding site, in addition to a well-established calcium/calmodulin site in the C-terminal autoregulatory domain. Unexpectedly, impairment of the basic loop interaction site completely abolishes calcium/calmodulin binding and DAPK2 activity is reduced to a residual level, indicative of coupled binding to the two sites. This contrasts with the generally accepted view that kinase calcium/calmodulin interactions are autonomous of the kinase catalytic domain. Our data establish an intricate model of multi-step kinase activation and expand our understanding of how calcium binding connects with other mechanisms involved in kinase activity regulation.

PubMed: 27133022
DOI: 10.1016/j.str.2016.03.020

Experimental method

X-RAY DIFFRACTION (1.47 Å)