Enhanced paper reading and huge kinase complexes
About a year ago we reported of PLoS and Molsoft launching a new way of publishing structural biology related papers. A couple of days ago I’ve stumbled on one such paper, published in PLoS biology and decided to take the technology for a ride.
Viewing the enhanced version of the paper demands a one time plug-in download which is rather fast. However, with the plug-in installed, it took the structural data a hefty 10 minutes to load. One possible reason for that, is the massive amount of structures solved by the authors – and this might be a good point to introduce the paper.
Calmodulin (or CaM) is a calcium dependent binding module. Amongst other targets, CaM binds CaMKII kinases and thus connects calcium signals to phosphorylation activated signaling pathways. These kinsases take key roles in many processes including signaling in neurons and controlling of the heart rate.
CaMKII forms an exceptionally large, dodecameric complex (long loading times or what ?). The authors solved the crystal structure of this complex for each of the four human CaMKII catalytic domains in complex with Ca2+/CaM, as well as the structure of the oligomerization domain (the part of the protein that mediates complex formation) in its physiological dodecameric state and in a tetradecameric(!!!!) state.
Enhanced paper reading
The solved complex structure captures the kinase in a novel state which together with analysis of structures of all human isozymes in their autoinhibited state, and in-solution association studies showed that binding of Ca2+/CaM triggers large structural changes in the kinase that together lead to allosteric kinase activation. Based on this, the authors propose a model that explains the substrate recognition leading to Ca2+/CaM-dependent allosteric activation of human CaMKIIs.
Besides the interesting biological story, the ‘enhanced reading’ feature is quite nice, and guides you along the reading. One major caveat though, is that anything other than simple rotation of the structure is not very intuitive (I still haven’t figured out how to zoom in and out). I hope in the future we’ll see more of these ‘enhanced’ papers and better controls. How were your impressions of this tool? Did anyone give it a go?
Rellos P, Pike AC, Niesen FH, Salah E, Lee WH, von Delft F, & Knapp S (2010). Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. PLoS biology, 8 (7) PMID: 20668654
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Andrew Wollacott
