EF-hand proteins

This review will focus on the large family of EF-hand proteins characterized by a common structural motif, the EF-hand (Fig 1). 

Kawasaki H, Nakayama S, Kretsinger RH (1998) Classification and evolution of EF-hand proteins. Biometals 11 277-295... 

Ikura, M. Calcium binding and conformational response in EF-hand proteins (1996) Trends Biochem. Sci. 21,14-17... 

Another group of calcium-buffering and storage proteins with remarkable Ca2+-binding properties are the 40- to 45-kDa calsequestrins, which are found in the lumen of the ER (sarcoplasmic reticulum) of skeletal muscle. Calsequestrins are not typical EF-hand proteins but have a high content of glutamate and aspartate. They bind 50 Ca2+ per molecule of protein with Kd 1 mM.104 105 Similar proteins called calreticulins are found in most non-muscle cells.106 107... 

A very large number of EF-hand proteins have... 

Vallely et al., 2002 Ikura and Ames, 2006). The C-terminal EF-hand contains the classical Ca2+-binding motif, common to all EF-hand proteins (see above). This Ca2+-binding motif has a typical sequence signature of 12 amino acids and is flanked by helices Hin and HIV. The N-terminal EF-hand is different from the classical EF-hand motif and is characteristic of the S100 proteins. Therefore, this EF-hand, with a 14 amino acid consensus sequence motif, is flanked by helices H, and Hn and is called the SlOO-specific or pseudo EF-hand. 

Filipek A, Jastrzebska B, Nowotny M, Kuznicki J. 2002a. CacyBP/SIP, a calcyclin and Siah-1-interacting protein, binds EF-hand proteins of the S100 family. J Biol Chem 277(32) 28848-28852. 

Fritz G, Mittl PR, Vasak M, Grutter MG, Heizmann CW. 2002. The crystal structure of metal-free human EF-hand protein S100A3 at 1.7-A resolution. J Biol Chem 277(36) 33092-33098. 

Gribenko AV, Hopper JE, Makhatadze GI. 2001. Molecular characterization and tissue distribution of a novel member of the S100 family of EF-hand proteins. Biochemistry 40(51) 15538-15548. 

Julenius K, Robblee J, Thulin E, Finn BE, Fairman R, Linse S. 2002. Coupling of ligand binding and dimerization of helix-loop-helix peptides spectroscopic and sedimentation analyses of calbindin D9k EF-hands. Proteins 47(3) 323-333. 

Marenholz I, Heizmann CW. 2004. S100A16, a ubiquitously expressed EF-hand protein which is up-regulated in tumors. Biochem Biophys Res Commun 313(2) 237—244. 

Imai Y, Ibata I, Ito D, Ohsawa K, Kohsaka S (1996) A novel gene ibal in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun 224 855-862 Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CN S injury by the stromal cell-derived factor lalpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101 18117-18122... 

A detailed survey of 276 sequences of EF-hand proteins has shown that 64% of the calcium-binding loops have fom acidic residues and 27% of the loops have three acidic residues at the ligand positions. Four acidic residues were... 

There are several major functional classes of EF-hand proteins. In the first class, trigger proteins like CaM and TnC bind calcium with a large change in protein... 

The published stractural studies show that nearly all the EF-hand proteins contain at least two interactive calciumbinding sites with average metal-metal distances of about... 

Different from trigger proteins, parvalbumin and calbindinD9k frmction as calcium-buffer proteins. Calcium binding to both proteins does not lead to conformational change with an exposed hydrophobic surface. The structure of a carp parvalbumin was the first structure in the EF-hand protein family. It has two isoforms (a and fi) with very similar stmctures. Oncomodulin is the mammahan beta hnkage parvalbumin. The stmcture of parvalbumin comprises three helix-loop-helix motifs, called AB, CD, and EF initially (Figure 11). The calcium-binding loop in the first... 

CBD is the smallest EF-hand protein with two EF-hand motifs. As a member of the S100 protein family, CBD contains one canonical and one pseudo-EF-hand motif at the C-terminus and N-terminus of the protein, respectively (Figure 11). Unlike other SI00 proteins, CBD remains monomeric in solution. Chazin and Forsen s groups have carried out extensive structural studies of CBD at different conditions. Tike parvalbumin, no significant stracture changes have been observed upon calcium binding. ... 

EF-hand proteins, each EF-hand motif of the penta-EF-hand proteins fhnctions separately withont cooperativity. Even if even-numbered calcium ions are bound, it is not necessary that they are paired. For example, in grancalcin and ALG-2, two calcium ions bind to EF-1 and EF-3 while the paired partners EF-2 and EF-4 are empty. hi24,i2s,i28... 

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