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Battle for the EF-hands: magnesium-calcium interference in calmodulin
A Malmendal1, S Linse, J Evenäs
1Physical Chemistry 2, Lund University, P.O. Box 124, S-221 00 Lund, Sweden. anders@scripps.edu
Biochemistry
|October 8, 1999
Summary
Magnesium ions (Mg2+) significantly reduce calcium ion (Ca2+) binding to calmodulin's N-terminal domain. This competition influences calmodulin's function, suggesting Ca2+ binding is linked to target molecule interaction.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Calmodulin (CaM) is a crucial Ca2+-regulatory protein.
- CaM activates enzymes in response to Ca2+ signals amidst high Mg2+ concentrations.
- The N-terminal domain of CaM exhibits low Ca2+ specificity, making Mg2+ competition significant.
Purpose of the Study:
- To investigate the interdependence of Ca2+ and Mg2+ binding in calmodulin's N-terminal domain.
- To elucidate the structural and dynamic consequences of Mg2+/Ca2+ competition.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy ((43)Ca, (1)H-(15)N).
- Fluorescent Ca2+ chelator techniques.
- Analysis of binding affinities and kinetic parameters.
Main Results:
- Physiological Mg2+ levels substantially decrease the apparent affinity for Ca2+ in the N-terminal domain.
- The (Ca2+)2 state is weakly populated at cellular Ca2+ levels, linking Ca2+ binding to target interaction.
- A mixed Mg2+/Ca2+ bound state ((Mg2+)1(Ca2+)1) is significantly populated and exhibits faster Ca2+ dissociation.
Conclusions:
- Mg2+ competition modulates Ca2+ binding to calmodulin's N-terminal domain.
- The (Mg2+)1(Ca2+)1 state adopts a conformation distinct from the fully Ca2+-bound state, resembling apo or Mg2+-bound states.
- These findings highlight the role of Mg2+ in regulating CaM's response to Ca2+ signals.