User:Alice Harmon/EF Hand
EF-hands are calcium-binding motifs found in hundreds of proteins. They bind calcium ions with high affinity (Kds are in the micromolar range) and selectivity, and this property allows EF-hand proteins to sense changes in intracellular calcium. In unstimulated cells cellular free calcium concentrations [Ca2+]c are in the nanomolar range (~10 nM in animal cells and ~200 nM in plant cells), and EF-hands are generally unoccupied by Ca2+. Upon stimulation, Ca2+ enters the cytosol from either outside the cell or from internal organelles, and [Ca2+]c rises to the micromolar range. EF-hands bind Ca2+, and this binding causes a conformational change that alters the activity of the protein.
This page focuses on the structure of EF hands. For additional information see http://en.wikipedia.org/wiki/EF_hand.
The name EF-hand originated from the first such structure to be described, which was in the protein parvalbumin[1]. In this protein calcium is bound by a helix-loop-helix structure that is formed by the E and F helices (letters assigned to helices in the order that they occur starting at the N-terminus). See the annotated protein sequence for carp parvalbumin here [1]. The structure resembled a hand with the forefinger pointing in the direction of the E helix, the thumb pointing in the direction of the H helix, and the remaining fingers curled to resemble the calcium-binding loop.
The EF-hand calcium-binding motif, which contains 12 residues, is defined in Prosite concensus pattern PS00018 [2]
| Residue | D-x-[DNS]-{ILVFYW}-[DENSTG]-[DNQGHRK]-{GP}-[LIVMC]-[DENQSTAGC]- x(2) -[DE] |
| Position | 1-2---3------4xxxx----5---------6------7-----8---------9-------10,11---12 |
where x indicates any residue; any residue in square brackets [] is possible at that position; none of the residues in curly brackets {} are possible: and x(2) indicates a series of two x.
The calcium ion is coordinated by seven oxygen atoms that form a pentagonal bipyramid (5 form the base of the pyramid and the others the points). One oxygen is contributed by each of the side chains of residues in positions 1, 3, 5, 9; two are from the side chain of E or D at position 12; one is from the backbone of the residue at position 7; and one from water.
From http://www.uniprot.org/manual/ca_bind Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand [1,2,3,4,5]. This type of domain consists of a twelve residue loop flanked on both side by a twelve residue α-helical domain (see <PDB:1CLL>). In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand). The basic structural/functional unit of EF-hand proteins is usually a pair of EF-hand motifs that together form a stable four-helix bundle domain. The pairing of EF-hand enables cooperativity in the binding of Ca2+ ions.
Below are EF-hands found in parvalbumin, calmodulin, and calcium-dependent protein kinase.
4cpv |
1prw |
3HX4 |