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. 

Figure 2.12 Two a helices that are connected by a short loop region in a specific geometric arrangement constitute a helix-turn-helix motif. Two such motifs are shown the DNA-binding motif (a), which is further discussed in Chapter 8, and the calcium-binding motif (b), which is present in many proteins whose function is regulated by calcium.

Nalefski, E.A., and FaUce, J.J., 1996, The C2 domain calcium-binding motif structural and functional diversity. Protein Sci. 5 2375-2390. 

The EGF-unit is defined by six conserved cysteines in a stretch of 35-40 amino acids CX7CX3 5CXio i2CXCX5GXRC, where C is cysteinej G, glycine R, arginine and X any other amino acid. The six cysteines form three disulphide bonds, C1-C3, C2-C4, and C5-C6. This motif is conserved in all EGF-like growth factors. Some of them contain calcium-binding motifs (for a review see ref. 36). 

FIGURE 17.20. An EF hand, a calcium-binding motif in proteins, (a) Ligands binding to each coordination position around Ca +, and (b) the sequence numbering (starting at 6 and proceeding to - -5) of the protein as it binds to Ca +... 

Tjoelker, L. W., Seyfried, C. E., Eddy, R. L., Byers, M. G., Shows, T. B., Calderon, J., Schreiber, R. B., and Gray, R W. (1994). Human, mouse, and rat calnexin cDNA cloning Identification of potential calcium binding motifs and gene localization to human chromosome 5. Biochemistry 33, 3229-3236. 

Proteins are constructed of modular systems or domains. These are portions of the polypeptide chain that can fold independendy into a stable structure. A protein may be just one domain, or may be comprised of many domains. A typical domain may be roughly 25 A in diameter and consist of 100-150 amino acid residues. For example, two a helices, joined by a loop (the helix-loop-helix motif) can give a calcium-binding motif or a DNA-binding motif. The so called Greek key motif consists of four antiparallel P strands arranged in a pattern reminiscent of one found in ancient Greekffiezes (80). The PaP motif consists of two P strands that are parallel but not necessarily adjacent connected by an a helix, which shields the strands from solvent. Some examples of these types of motifs are shown in Fig. 33. 

Fig. 15.11. Ribbon diagrams [54]. Left calcium-binding motif (residues 78-108) of carp parval-bumin (4CPV) right DNA binding motif (residues 168-191) of catabolite gene activator protein (3 GAP)...

Several calcium-binding motifs have been characterized for proteins especially those with regulatory roles. The structural chemistry of EF hands and the coordination chemistry of calcium and other spherical metal ions, and related models, have been reviewed by Falke. " ... 

EF-hand Calcium-binding motif originally identified in the... 

One calcium-binding motif found in proteins is the helixloophelix motif, also known as an EF hand [74, 75]. A comparison, diagrammed in Fig. 29, is made... 

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