EF‐hand Calcium‐binding Proteins

Melanie R Nelson, Ambrx, La Jolla, California, USA
Benjamin Chagot, Vanderbilt University, Nashville, Tennessee, USA
Walter J Chazin, Vanderbilt University, Nashville, Tennessee, USA

Published online: January 2010

DOI: 10.1002/9780470015902.a0003056.pub2

Calcium and the proteins that bind to it play important roles in normal physiological processes and have been implicated in a variety of diseases. The importance of calcium is due mainly to its role as a second messenger in signal transduction. The calcium signal is mediated and controlled by many proteins in the cell, the majority of which belong to the EF-hand super-family of calcium-binding proteins. EF-hand proteins are classified into calcium signal sensors and modulators. The calcium modulators fine-tune the shape and duration of calcium signals. The sensors undergo significant conformational changes when they bind calcium, which exposes new surfaces that interact with target proteins. Together, EF-hand calcium-binding proteins serve in the critical process of converting the ionic signal into activation of signalling pathways in cells.

Key Concepts:

  • The EF-hand is a helix–loop–helix structural motif.
  • Calcium binds to oxygen atoms from the backbone and side-chain atoms of specific amino acids in EF-hand calcium-binding proteins.
  • The basic structural and functional unit of EF-hand calcium-binding proteins is a pair of EF-hand motifs.
  • EF-hand calcium-binding proteins can be classified as sensors or modulators of calcium signals.
  • EF-hand calcium senor proteins need to transition from an ‘off ’ state at the resting level of calcium in the cell, to an ‘on’ (activated) state when calcium signals increase the concentration of calcium.
  • The activation of EF-hand calcium sensor proteins results from changes in structure induced by the binding of calcium ions.
  • The binding of calcium activates EF-hand calcium sensor proteins, triggering their interaction with target proteins.

Keywords: calcium; protein; signal transduction; calmodulin

Figure 1. (a) The consensus sequence of the canonical EF-hand is mapped onto a schematic representation of the helix–loop–helix motif. X, Y, Z and –Z are side-chain oxygen ligands, the hashmark indicates the backbone carbonyl ligand, and –X is a water ligand that is hydrogen-bonded to a loop residue. Asterisk indicates that any residue can occupy the position and ‘n’ indicates that any hydrophobic residue can occupy the position. (b) The calcium ligation geometry is shown with a ribbon representation of the loop from the first EF-hand of calmodulin (PDB code 1CLL). The ligating oxygen atoms of amino acids are shown black. Ligation is indicated by dotted lines, the pyramidal plane is indicated by the solid lines, and the hydrogen bond to the ligating water molecule is indicated by a dot-dashed line.
Figure 2. Schematic representation of (a) the EF-hand motif, (b) a two-EF-hand calcium-binding unit and (c) two examples of the organization of the calcium-binding unit in proteins.
Figure 3. Ribbon representation showing how target binding induces changes in the quarternary structure of calmodulin. The conformation of the two domains of calmodulin is unaffected by target binding, but the orientation of the domains with respect to each other changes drastically, bringing the two previously independent domains into contact. Calcium-loaded calmodulin (PDB code 1CLL) is shown at the top, and calcium-loaded calmodulin complexed with a peptide derived from smooth-muscle myosin light chain kinase (PDB code 1CDL) is shown at the bottom. The N-terminal domain of calmodulin is medium blue, the C-terminal domain is dark blue, and the linker loop between the domains is light blue. The peptide is red, and the calcium ions are represented as yellow balls. The tint indicates the Connolly surfaces of the molecules.
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    Marenholz I, Heizmann CW and Fritz G (2004) S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochemical and Biophysical Research Communications 322: 1111–1122.
    book Van Eldik L and Watterson DM (eds) (1998) Calmodulin and Signal Transduction. New York: Academic Press.

Related Sub-Topics:

Intracellular and Extracellular Signalling | Signal Transduction | Protein Structure | Biomolecular Interactions | Proteins: Structure, Function, Metabolism
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Article Title: EF‐hand Calcium‐binding Proteins
 
How to Cite close
Nelson, Melanie R, Chagot, Benjamin, and Chazin, Walter J(Jan 2010) EF‐hand Calcium‐binding Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003056.pub2]