User:Michael Roberts/BIOL115 CaM: Difference between revisions

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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'll 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 α-helices joined by loops. A helix-loop-helix motif forms the basis of each EF hand.

'''MOLECULAR MODEL''':

Colour key:

In each EF hand loop, the ^Ca2+ ions are bound by amino acid residues in and near the loops.

The structure shown here has four <scene name='User:Michael_Roberts/BIOL115_CaM/Structure_plus_c/3'>^Ca2+ ions</scene> 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.

To illustrate how ^Ca2+  is bound, this display shows the <scene name='User:Michael_Roberts/BIOL115_CaM/Co-ordination/1'>residues that take part in binding</scene> one of the ^Ca2+ ions.

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 <scene name='User:Michael_Roberts/BIOL115_CaM/Co-ordination/3'>seven oxygen</scene> 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 <scene name='User:Michael_Roberts/BIOL115_CaM/Inactive_calmodulin/1'>its structure </scene>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.

The Ca2+-bound form of calmodulin with its exposed hydrophobic surfaces that you have already observed can <scene name='User:Michael_Roberts/BIOL115_CaM/Active_calmodulin/1'>interact with a target protein</scene>. It does this by wrapping around a specific sequence on the target molecule, forcing it to adopt an a-helical structure.  

You can view a nice animation of the conformational change undergone by calmodulin upon calcium binding by following this link [http://www.molmovdb.org/cgi-bin/morph.cgi?ID=b097743-28520].