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Updated: Aug 13, 2026

Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: two ways to promote
Mitsuhiko Ikura1, James B Ames
1Division of Signaling Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. mikura@uhnres.utoronto.ca
Abstract:
Calcium signaling pathways control a variety of cellular events such as gene transcription, protein phosphorylation, nucleotide metabolism, and ion transport. These pathways often involve a large number of calcium-binding proteins collectively known as the calmodulin or EF-hand protein superfamily. Many EF-hand proteins undergo a large conformational change upon binding to Ca(2+) and target proteins. All members of the superfamily share marked sequence homology and similar structural features required to sense Ca(2+). Despite such structural similarities, the functional diversity of EF-hand calcium-binding proteins is extraordinary. Calmodulin itself can bind >300 different proteins, and the many members of the neuronal calcium sensor and S100 protein families collectively recognize a largely different set of target proteins. Recent biochemical and structural studies of many different EF-hand proteins highlight remarkable similarities and variations in conformational responses to the common ligand Ca(2+) and their respective cellular targets. In this review, we examine the essence of molecular recognition activities and the mechanisms by which calmodulin superfamily proteins control a wide variety of Ca(2+) signaling processes.
Insights
Calcium signaling relies on EF-hand proteins, like calmodulin, which change shape to interact with diverse cellular targets. This review explores how these calcium-binding proteins achieve functional diversity through molecular recognition.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Signaling
Background:
- Calcium signaling pathways regulate crucial cellular events including gene transcription and ion transport.
- These pathways involve calcium-binding proteins, collectively termed the calmodulin or EF-hand protein superfamily.
- EF-hand proteins share structural similarities for calcium sensing but exhibit extraordinary functional diversity.
Purpose of the Study:
- To review the molecular recognition activities of calmodulin superfamily proteins.
- To elucidate the mechanisms by which these proteins control calcium (Ca2+) signaling processes.
- To highlight similarities and variations in conformational responses to Ca2+ binding.
Main Methods:
- Review of recent biochemical and structural studies.
- Analysis of sequence homology and structural features.
- Examination of protein-ligand interactions and conformational changes.
Main Results:
- EF-hand proteins undergo significant conformational changes upon Ca2+ binding.
- Calmodulin interacts with over 300 different proteins.
- Neuronal calcium sensor and S100 protein families recognize distinct sets of target proteins.
Conclusions:
- Despite conserved structural features, EF-hand proteins display remarkable functional diversity.
- Molecular recognition mechanisms are key to the varied roles of calmodulin superfamily proteins in Ca2+ signaling.
- Understanding these mechanisms is crucial for deciphering cellular event regulation.
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