User:Michael Roberts/BIOL115 CaM
Sequence and structure of EF hands
The EF hand motif is present in a many proteins and it commonly bestows the ability to bind Ca2+ ions. It was first identified in parvalbumin, a muscle protein. Here we will have a look at the Ca2+-binding protein calmodulin, which possesses four EF hands. Calmodulin and its isoform, troponinC, are important intracellular Ca2+-binding proteins.
The structure below, obtained by X-ray crystallography, represents the Ca2+-binding protein calmodulin. It has a dumbell-shaped structure with two identical lobes connected by a central alpha-helix. Each lobe comprises three a helices joined by loops. A helix-loop-helix motif forms the basis of each EF hand.
Click on the 'green links' in the text in the scrollable section below to examine this molecule in more detail.
Let's start with a simple of the protein. This shows all the bonds between the atoms that make up the protein.
BACKBONE: The wireframe view shows us all the atoms, but this can be too much detail if we're mainly interested ion the overall structure of the protein. This next veiw takes us right doewn to a minimal representation that simply traces the of the protein. The backbone includes the peptide linkages between each amino acid, along with the alpha-carbon atoms to which the side chains are attached. Notice that helical regions can now be seen.
SECONDARY STRUCTURE: This is shown more clearly by a . The computer calculates where regions of secondary structure occur and draws them as ribbons. The alpha-helical region is now clearly defined, and there are also regions of beta-structure. Colour key: Alpha Helices, Beta Strands . The short anti-parallel beta-sheet between the adjacent EF hand loops are observed in calmodulins from various species.
CALCIUM IONS: In each EF hand loop, the Ca2+ ions are bound by residues in and near the loops. The structure shown has four bound. In this condition, the protein adopts the extended structure shown. The EF hand-forming helices are bent away from the long linking helix, revealing hydrophobic residues and exposing the linking chain.
CO-ORDINATING RESIDUES: To illustrate how Ca2+ is bound, this display shows the that take part in binding one of the Ca2+ ions. to see this more clearly.
CO-ORDINATING ATOMS: To highlight the atoms that co-ordinate the Ca2+ ion, we can now enlarge those that are close (within 2.7 Å). This shows that atoms form the calcium co-ordination shell. Five are contributed by the side chain carboxyl groups of Asp and Glu and a sixth by the peptide carbonyl of Gln. The seventh oxygen is provided by an associated water molecule.
INACTIVE CALMODULIN: At resting levels of cytosolic Ca2+ (~100 nM), calmodulin exists predominantly in the calcium-free form. This is called apo-calmodulin and is more compact. The terminal helices are folded down concealing their hydrophobic surfaces and the central chain, which is not a helical along its whole length, is not exposed. CALMODULIN INTERACTS WITH ITS TARGET: The Ca2+-bound form of calmodulin with its exposed hydrophobic surfaces that you have already observed can . It does this by wrapping around a specific sequence on the target molecule, forcing it to adopt an a-helical structure. The target molecule here is the calmodulin-regulated enzyme, myosin light chain kinase. Only a short sequence from this protein, the calmodulin binding domain, is shown. End of section |
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