3KK8

CaMKII Substrate Complex A

Summary for 3KK8

• Entry DOI: 10.2210/pdb3kk8/pdb
• Related: 3KK9 3KL8
• Descriptor: Calcium/calmodulin dependent protein kinase II, MAGNESIUM ION (3 entities in total)
• Functional Keywords: protein kinase, atp-binding, kinase, nucleotide-binding, serine/threonine-protein kinase, transferase
• Biological source: Caenorhabditis elegans (nematode)
• Total number of polymer chains: 1
• Total formula weight: 32227.89

Authors

Kuriyan, J.,Chao, L.H.,Pellicena, P.,Deindl, S.,Barclay, L.A.,Schulman, H. (deposition date: 2009-11-04, release date: 2010-02-09, Last modification date: 2021-10-13)

Primary citation

Chao, L.H.,Pellicena, P.,Deindl, S.,Barclay, L.A.,Schulman, H.,Kuriyan, J.
Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation.
Nat.Struct.Mol.Biol., 17:264-272, 2010

PubMed Abstract: The dodecameric holoenzyme of calcium-calmodulin-dependent protein kinase II (CaMKII) responds to high-frequency Ca(2+) pulses to become Ca(2+) independent. A simple coincidence-detector model for Ca(2+)-frequency dependency assumes noncooperative activation of kinase domains. We show that activation of CaMKII by Ca(2+)-calmodulin is cooperative, with a Hill coefficient of approximately 3.0, implying sequential kinase-domain activation beyond dimeric units. We present data for a model in which cooperative activation includes the intersubunit 'capture' of regulatory segments. Such a capture interaction is seen in a crystal structure that shows extensive contacts between the regulatory segment of one kinase and the catalytic domain of another. These interactions are mimicked by a natural inhibitor of CaMKII. Our results show that a simple coincidence-detection model cannot be operative and point to the importance of kinetic dissection of the frequency-response mechanism in future experiments.

PubMed: 20139983
DOI: 10.1038/nsmb.1751

Experimental method

X-RAY DIFFRACTION (1.72 Å)