Salt enhances calmodulin-target interaction
Ingemar André 1*, Tõnu Kesvatera 2, Bo Jönsson 3 and Sara Linse 1
1 Department of Biophysical Chemistry, Lund University
2 Laboratory of Bioorganic Chemistry, National Institute of Chemical Physics and Biophysics, Estonia
3 Department of Theoretical Chemistry, Lund University
* To whom correspondence should be addressed. E-mail: ingemar.andre{at}bpc.lu.se.
Submitted on June 15, 2005
Revised on July 19, 2005
Accepted on 22 December 2005
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Abstract |
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Calmodulin (CaM) operates as a Ca2+ sensor and is known to interact with and regulate a large number of proteins involved in a great many aspects of cellular function. It is of considerable interest to understand the balance of forces in complex formation of CaM with its target proteins. Here we have studied the importance of electrostatic interactions in the complex between CaM and a peptide derived from smooth muscle myosin light chain kinase by experimental methods and Monte Carlo simulations of electrostatic interactions. We show by MC simulations that, in agreement with experimental data, the binding affinity between CaM and highly charged peptides is surprisingly insensitive to changes in the net charge of both the protein and peptide. We observe an increase in the binding affinity between oppositely charged partners with increasing salt concentration from zero to 100 mM showing that formation of globular CaM-kinase type complexes is facilitated at physiological ionic strength. We conclude that ionic interactions in complex formation are optimized at pH and saline similar to the cell environment, which probably overrules the electrostatic repulsion between the negatively charged Ca2+-binding domains of CaM. We propose a conceivable rationalization of CaM electrostatics associated with inter-domain repulsion.
Key Words:
CaM-peptide, Electrostatic interactions, Monte-Carlo simulation
