Summary
PDB 2VZ6 deposited: 2008-07-30 modified: 2011-08-10
Title STRUCTURE OF HUMAN CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE TYPE II ALPHA (CAMK2A) IN COMPLEX WITH INDIRUBIN E804
Authors Knapp, S., Lee, W.H., Niesen, F.H., Pike, A.C.W., Rellos, P., Salah, E., Von Delft, F.
Method X-RAY DIFFRACTION
Structure factors resolution 2.3 rfactor 0.163 rfree 0.203
DPI 0.41 theoretical min: 0.23
Related PDB Entries 2UX0 2V7O 2VN9 2W2C 2WEL
Citations

UNLABELLED: 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. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

Plos Biol. 2010 ; 8(7):426- doi:10.1371/JOURNAL.PBIO.1000426

Cross References
Database source Identifier Description
PubMed 20668654
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2VZ6/1 2VZ6 1 monomer 0 1 3 2223
2VZ6/2 2VZ6 2 monomer 0 1 2 2205