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 - 4 - 5 - 6 - 7 - 8 - 9 -10,11 - 12 |
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 |