Structural highlights
Function
[KCC2A_RAT] CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity.[1]
Publication Abstract from PubMed
The Ca2+/calmodulin-dependent protein kinase II (CaMKII) assembles into large 12-meric holoenzymes, which is thought to enable regulatory processes required for synaptic plasticity underlying learning, memory and cognition. Here we used single particle electron microscopy (EM) to determine a pseudoatomic model of the CaMKIIalpha holoenzyme in an extended and activation-competent conformation. The holoenzyme is organized by a rigid central hub complex, while positioning of the kinase domains is highly flexible, revealing dynamic holoenzymes ranging from 15-35 nm in diameter. While most kinase domains are ordered independently, approximately 20% appear to form dimers and <3% are consistent with a compact conformation. An additional level of plasticity is revealed by a small fraction of bona-fide 14-mers (<4%) that may enable subunit exchange. Biochemical and cellular FRET studies confirm that the extended state of CaMKIIalpha resolved by EM is the predominant form of the holoenzyme, even under molecular crowding conditions.
The CaMKII holoenzyme structure in activation-competent conformations.,Myers JB, Zaegel V, Coultrap SJ, Miller AP, Bayer KU, Reichow SL Nat Commun. 2017 Jun 7;8:15742. doi: 10.1038/ncomms15742. PMID:28589927[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Krapivinsky G, Medina I, Krapivinsky L, Gapon S, Clapham DE. SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron. 2004 Aug 19;43(4):563-74. PMID:15312654 doi:10.1016/j.neuron.2004.08.003
- ↑ Myers JB, Zaegel V, Coultrap SJ, Miller AP, Bayer KU, Reichow SL. The CaMKII holoenzyme structure in activation-competent conformations. Nat Commun. 2017 Jun 7;8:15742. doi: 10.1038/ncomms15742. PMID:28589927 doi:http://dx.doi.org/10.1038/ncomms15742
