The role of electrostatic interactions in calmodulin-peptide complex formation

Biophysical Journal
Ingemar AndréSara Linse

Abstract

The complex between calmodulin and the calmodulin-binding portion of smMLCKp has been studied. Electrostatic interactions have been anticipated to be important in this system where a strongly negative protein binds a peptide with high positive charge. Electrostatic interactions were probed by varying the pH in the range from 4 to 11 and by charge deletions in CaM and smMLCKp. The change in net charge of CaM from approximately -5 at pH 4.5 to -15 at pH 7.5 leaves the binding constant virtually unchanged. The affinity was also unaffected by mutations in CaM and charge substitutions in the peptide. The insensitivity of the binding constant to pH may seem surprising, but it is a consequence of the high charge on both protein and peptide. At low pH it is further attenuated by a charge regulation mechanism. That is, the protein releases a number of protons when binding the positively charged peptide. We speculate that the role of electrostatic interactions is to discriminate against unbound proteins rather than to increase the affinity for any particular target protein.

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Citations

Feb 7, 2013·ACS Chemical Neuroscience·Nikolai SlavovSara Linse
Jul 2, 2008·Journal of Proteome Research·Amina S WoodsKjell Fuxe
Jan 14, 2010·Molecular & Cellular Proteomics : MCP·David J O'ConnellDolores J Cahill
May 11, 2012·Journal of Biomolecular Structure & Dynamics·Krzysztof Kuczera, Petri Kursula
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