Salt enhances calmodulin-target interaction

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Salt enhances calmodulin-target interaction. / André, Ingemar; Kesvatera, Tönu; Jönsson, Bo; Linse, Sara.

In: Biophysical Journal, Vol. 90, No. 8, 2006, p. 2903-2910.

Research output: Contribution to journalArticle

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TY - JOUR

T1 - Salt enhances calmodulin-target interaction

AU - André, Ingemar

AU - Kesvatera, Tönu

AU - Jönsson, Bo

AU - Linse, Sara

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Biophysical Chemistry (LTH) (011001011), Theoretical Chemistry (S) (011001039)

PY - 2006

Y1 - 2006

N2 - Calmodulin (CaM) operates as a Ca2+ sensor and is known to interact with and regulate hundreds 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 Monte Carlo 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 interdomain repulsion.

AB - Calmodulin (CaM) operates as a Ca2+ sensor and is known to interact with and regulate hundreds 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 Monte Carlo 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 interdomain repulsion.

U2 - 10.1529/biophysj.105.068718

DO - 10.1529/biophysj.105.068718

M3 - Article

VL - 90

SP - 2903

EP - 2910

JO - Biophysical Journal

JF - Biophysical Journal

SN - 1542-0086

IS - 8

ER -