Parvalbumin, 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. 

Parvalbumin is another protein in search of a function. It contains three HLH motifs (Mr 1 IK), but only the second and third are functional Ca " -binding sites. These are high-affinity Ca /Mg sites, and both are filled with Ca in the known crystal structures (references in Table I). In fast twitch muscle, where most parvalbumins are found, the protein is postulated to act as a Ca " buffer (Haich a/., 1979 Gi s etal., 1982). As Ca is released from troponin C after muscle contraction, the Ca may be bound by parvalbumin to prevent reinitiation of contraction. In resting cells parvalbumin likely binds Mg ", rather than Ca (Haiech etal., 1979). 

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. ... 

Parvalbumins, water-soluble, monomeric proteins (Mr 12 kDa) with high-affinity sites for Ca +, predominantly found in the skeletal muscle of vertebrates. The parvalbumins also bind Mg + competitively. They occur not only in skeletal muscle of fish and amphibia, but also in mammalian muscle. Parvalbumins are related in structure and function to calmodulin and troponin C. They contain six o -helical regions (A to F), and the binding sites for two Ca + are formed by helix-loop-helix motifs (EF hands) between helices C/D and E/F. Human alpha and beta parvalbumins belong to the EF-hand type proteins [C. H. Heizmann, Experientia 1984, 40,910 U. G. Fohr et al., Eur.]. Biochem. 1993, 215, 719]. 

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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