Abstract
The paper reports the results of numerical calculations of the pKa’s of the ionizable groups and the electrostatic interactions between calmodulin lobes in three different states of calmodulin: calcium-free, peptide-free; calcium-loaded, peptide-free; and calcium-loaded, peptide-bound. NMR and X-ray studies revealed that in these states the overall structure of calmodulin adopts various conformations referred as: disordered semi-compact, extended and compact conformations, respectively. In addition, a new X-ray structure was recently reported (Structure, 2003, 11, 1303) showing that calcium-loaded, peptide-free calmodulin can also adopt a compact conformation in addition to the well known extended conformation. The calculated energy changes of calcium-loaded, peptide-free calmodulin along the pathway connecting these two conformations provide a possible explanation for this structural plasticity. The effect of pH and organic compounds in the solution phase on the preference of calmodulin to adopt compact or extended conformations may be thus rationalized. Analysis of the contribution of the ionization changes to the energy of association of calmodulin lobes suggested that the formation of the compact forms requires protonation of several acidic residues. However, two different protonation scenarios are revealed: a protonation due to internal lobe organization and thus independent of the lobes association, and a protonation induced by the lobes association resulting to a proton uptake. In addition, the role of the individual residues on the energy of association of calmodulin lobes is calculated in two compact conformations (peptide-free and peptide-bound) and is shown that a set of residues always plays a dominant role in inter-domain interactions.
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Abbreviations
- CaM:
-
Calmodulin
- CFPF:
-
Calcium-free, peptide-free
- CLPF:
-
Calcium-loaded, peptide-free
- CLPB:
-
Calcium-loaded, peptide-bound
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Isvoran, A., Craescu, C.T. & Alexov, E. Electrostatic control of the overall shape of calmodulin: numerical calculations. Eur Biophys J 36, 225–237 (2007). https://doi.org/10.1007/s00249-006-0123-1
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DOI: https://doi.org/10.1007/s00249-006-0123-1