2UX0

Structure of the oligomerisation domain of calcium-calmodulin dependent protein kinase II gamma

Summary for 2UX0

• Entry DOI: 10.2210/pdb2ux0/pdb
• Descriptor: CALCIUM-CALMODULIN DEPENDENT PROTEIN KINASE (CAM KINASE) II GAMMA, GLYCINE (3 entities in total)
• Functional Keywords: transferase, calmodulin, protein kinase, oligomerisation domain, serine- threonine kinase, atp-binding, kinase, nucleotide-binding, serine/threonine-protein kinase, transferase.
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 6
• Total formula weight: 98627.69

Authors

Bunkoczi, G.,Debreczeni, J.E.,Salah, E.,Gileadi, O.,Rellos, P.,Arrowsmith, C.H.,Edwards, A.,Sundstrom, M.,Weigelt, J.,von Delft, F.,Turnbull, A.,Pike, A.C.W.,Knapp, S. (deposition date: 2007-03-26, release date: 2007-04-10, Last modification date: 2023-12-13)

Primary citation

Rellos, P.,Pike, A.C.W.,Niesen, F.H.,Salah, E.,Lee, W.H.,von Delft, F.,Knapp, S.
Structure of the Camkiidelta/Calmodulin Complex Reveals the Molecular Mechanism of Camkii Kinase Activation.
Plos Biol., 8:426-, 2010

PubMed Abstract: Long-term potentiation (LTP), a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM)-dependent kinase II (CaMKII). CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.

PubMed: 20668654
DOI: 10.1371/JOURNAL.PBIO.1000426

Experimental method

X-RAY DIFFRACTION (2.46 Å)