EF hand

(Redirected from EF-hand)
Jump to: navigation, search
EF hand
File:Calmodulin 1CLL.png
Calmodulin with four EF-Hand-motifs.
Identifiers
Symbolefhand
PfamPF00036
InterProIPR002048
PROSITEPDOC00018
SCOP1osa
SUPERFAMILY1osa
OPM protein1djx


The EF hand is a helix-turn-helix structural domain found in a large family of calcium-binding proteins. It consists of two alpha helices positioned roughly perpendicular to one another and linked by a short loop region (usually about 12 amino acids) that usually binds calcium ions. The motif takes its name from traditional nomenclature used in describing the protein parvalbumin, which contains three such motifs and is probably involved in muscle relaxation via its calcium-binding activity. EF hands also appear in each structural domain of the signaling protein calmodulin and in the muscle protein troponin-C.

Binding site

The calcium ion is bound by both protein backbone atoms and by amino acid side chains, specifically those of the acidic amino acid residues, aspartate and glutamate. These residues are negatively charged and will make a charge-interaction with the positively charged calcium ion. The EF hand motif was among the first structural motifs whose sequence requirements were analyzed in detail. Five of the loop residues bind calcium and thus have a strong preference for oxygen-containing side chains, especially aspartate and glutamate. The sixth residue in the loop is necessarily glycine due to the conformational requirements of the backbone. The remaining residues are typically hydrophobic and form a hydrophobic core that binds the stabilizes the two helices.

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).

Classification

The EF-hands can be divided into two classes: signaling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.

Subfamilies

Human proteins containing this domain

ACTN1; ACTN2; ACTN3; ACTN4; APBA2BP; AYTL1; AYTL2; C14orf143; CABP1; CABP2; CABP3; CABP4; CABP5; CABP7; CALB1; CALB2; CALM2; CALM3; CALML3; CALML4; CALML5; CALML6; CALN1; CALU; CAPN1; CAPN11; CAPN2; CAPN3; CAPN9; CAPNS1; CAPNS2; CAPS; CAPS2; CAPSL; CBARA1; CETN1; CETN2; CETN3; CHP; CHP2; CIB1; CIB2; CIB3; CIB4; CRNN; DGKA; DGKB; DGKG; DST; DUOX1; DUOX2; EFCAB1; EFCAB2; EFCAB4A; EFCAB4B; EFCAB6; EFCBP1; EFCBP2; EFHA1; EFHA2; EFHB; EFHC1; EFHD1; EFHD2; EPS15; EPS15L1; FKBP10; FKBP14; FKBP7; FKBP9; FKBP9L; FREQ; FSTL1; FSTL5; GCA; GPD2; GUCA1A; GUCA1B; GUCA1C; hippocalcin; HPCAL1; HPCAL4; HZGJ; IFPS; ITSN1; ITSN2; KCNIP1; KCNIP2; KCNIP3; KCNIP4; KIAA1799; LCP1; MACF1; MRLC2; MRLC3; MST133; MYL1; MYL2; MYL5; MYL6B; MYL7; MYL9; MYLC2PL; MYLPF; NCALD; NIN; NKD1; NKD2; NLP; NOX5; NUCB1; NUCB2; OCM; PDCD6; PEF1; PKD2; PLCD1; PLCD4; PLCH1; PLCH2; PLS1; PLS3; PP1187; PPEF1; PPEF2; PPP3R1; PPP3R2; PRKCSH; PVALB; RAB11FIP3; RASEF; RASGRP; RASGRP1; RASGRP2; RASGRP3; RCN1; RCN2; RCN3; RCV1; RCVRN; REPS1; RHBDL3; RHOT1; RHOT2; RPTN; RYR2; RYR3; S100A1; S100A11; S100A12; S100A6; S100A8; S100A9; S100B; S100G; S100Z; SCAMC-2; SCGN; SDF4; SLC25A12; SLC25A13; SLC25A23; SLC25A24; SLC25A25; SPATA21; SPTA1; SPTAN1; SRI; TBC1D9; TBC1D9B; TCHH; TESC; TNNC1; TNNC2; USP32; VSNL1; ZZEF1;

See also

Another distinct calcium-binding motif composed of alpha helices is the dockerin domain.

External links

Further reading

  • Branden C, Tooze J. (1999). Introduction to Protein Structure 2nd ed. Garland Publishing: New York, NY.
  • Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories. Nakayama S, Moncrief ND, Kretsinger RH; J Mol Evol 1992;34:416-448. PMID 1602495
  • Comparison of terbium (III) luminescence enhancement in mutants of EF hand calcium binding proteins. Hogue CW, MacManus JP, Banville D, Szabo AG; J Biol Chem 1992;267:13340-13347. PMID 1618836
  • EF-hand motifs in inositol phospholipid-specific phospholipase C. Bairoch A, Cox JA; FEBS Lett 1990;269:454-456.PMID 2401372
  • The evolving model of calmodulin structure, function and activation. Finn BE, Forsen S; Structure 1995;3:7-11. PMID 7743133


Protein secondary structure
Helices: α-helix | 310 helix | π-helix | β-helix | Polyproline helix | Collagen helix
Extended: β-strand | Turn | Beta hairpin | Beta bulge | α-strand
Supersecondary: Coiled coil | Helix-turn-helix | EF hand
Secondary structure propensities of amino acids
Helix-favoring: Methionine | Alanine | Leucine | Glutamic acid | Glutamine | Lysine
Extended-favoring: Threonine | Isoleucine | Valine | Phenylalanine | Tyrosine | Tryptophan
Disorder-favoring: Glycine | Serine | Proline | Asparagine | Aspartic acid
No preference: Cysteine | Histidine | Arginine
←Primary structure Tertiary structure→


de:EF-Hand


Linked-in.jpg