Parvalbumin calcium-binding motif

One of these motifs, called the helix-turn-helix motif, is specific for DNA binding and is described in detail in Chapters 8 and 9. The second motif is specific for calcium binding and is present in parvalbumin, calmodulin, tro-ponin-C, and other proteins that bind calcium and thereby regulate cellular activities. This calcium-binding motif was first found in 1973 by Robert Kretsinger, University of Virginia, when he determined the structure of parvalbumin to 1.8 A resolution. 

Parvalbumin is a muscle protein with a single polypeptide chain of 109 amino acids. Its function is uncertain, but calcium binding to this protein probably plays a role in muscle relaxation. The helix-loop-helix motif appears three times in this structure, in two of the cases there is a calcium-binding site. Figure 2.13 shows this motif which is called an EF hand because the fifth and sixth helices from the amino terminus in the structure of parvalbumin, which were labeled E and F, are the parts of the structure that were originally used to illustrate calcium binding by this motif. Despite this trivial origin, the name has remained in the literature. 

The calcium binding proteins calbindin D28k, calretinin and parvalbumin are members of a family of proteins characterized by the presence of calcium binding EF-hand motifs, modulated by stimulus-induced increases in cytosolic free calcium ions (Persechini et ah,... 

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... 

Figure 11 Structures of (a) parvalbumin and (b) CBD. Parvalbumin contains three EF-hand motifs, two of them bind to calciiun (purple) and one loses the calcium-binding ability (orange). CBD is monomer while the other SI00 proteins are dimer ...

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. ... 

In summary, the ranking was successful in that the known calcium-binding folds of troponin-C, calcium-binding parvalbumin B and calmodulin were contained within the top six ranking positions. An inspection of the distance distributions for these six structures reveals a substantial degree of similarity with the distribution for the query motif, and similar comments apply to the ICLN hits ranked seventh and eighth. After this, however, the distributions become markedly dissimilar. 

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