Muscle calcium binding proteins

R. H. Kretsinger and C. F. Nockolds, Carp muscle calcium-binding protein, J. Biol. Chem. 248, 3313-3326 (1973). 

Fig. 56. The calcium-binding sites from carp muscle calcium-binding protein (a) backbone of the entire E-F hand (b) detailed view of the E-F calcium-binding site, including those side chains which are Ca ligands (c) detailed view of the C-D calcium-binding site, rotated to match part b. Oxygens are shown as open circles and a-carbons as solid dots.

Cytochrome c peroxidase domain 1 C. Miscellaneous antiparallel a Carp muscle calcium-binding protein Egg lysozyme Citrate synthase Catalase domain 2 Cytochrome c peroxidase domain 2 p-Hydroxybenzoate hydroxylase domain 3 II. Parallel a/j3 domains... 

Kretsinger, R. H. (1972). Gene triplication deduced from the tertiary structure of a muscle calcium binding protein. Nature (London) New Biol. 240,85-88. 

Compounds with vitamin K activity (Table 6.2) are required in our diets for y-carboxyglutamate biosynthesis (Table 4.1). This amino acid is produced from certain protein glutamyl residues by carboxylation. Proteins that contain y-carboxyglutamate are blood prothrombin and coagulation factors VII, IX, and X (see Chapter 7). Other proteins of this type are osteocalcin from bone and several kidney and muscle calcium-binding proteins. 

III. AMINO ACID COMPOSITION OF SMOOTH MUSCLE CALCIUM BINDING PROTEINS... 

Bauer, D. R., Opella, S. J., Nelson, D. J., and Pecora, R. (1975)./. Amer. Chem. Soc. 97, 2580. Depolarized Light Scattering and Carbon Nuclear Resonance Measurements of the Isotropic Rotational Correlation Time of Muscle Calcium Binding Protein. 

Figure 3. The muscle calcium binding protein molecule has the general shape of a prolate ellipsoid of revolution (59). The shell, 2.7-A thick, contains those atoms, exclusive of hydrogen, that would be exposed to the solvent were there no surface indentations. The oblate ellipsoid hydrocarbon core consists of side chains of phenylalanine, leucine, isoleucine, and valine.

Kretsinger, R.H., Nockolds, C.E. 1973. Carp muscle calcium-binding protein. II. Stracture determination and general description. J Biol Chem. 248 3313-26. 

BPTI, bovine pancreatic trypsin inhibitor MCBP, muscle calcium binding protein... 

Sorcin (soluble resistance-related calcium binding protein) was isolated from multidrug-resistant cells and is expressed in a few mammalian tissues such as skeletal muscle, heart, and brain. In the heart, sorcin interacts with the ryanodine receptor and L-type Ca2+-channels regulating excitation in contraction coupling. 

In striated muscle, there are two other proteins that are minor in terms of their mass but important in terms of their function. Tropomyosin is a fibrous molecule that consists of two chains, alpha and beta, that attach to F-actin in the groove between its filaments (Figure 49-3). Tropomyosin is present in all muscular and muscle-fike structures. The troponin complex is unique to striated muscle and consists of three polypeptides. Troponin T (TpT) binds to tropomyosin as well as to the other two troponin components. Troponin I (Tpl) inhibits the F-actin-myosin interaction and also binds to the other components of troponin. Troponin C (TpC) is a calcium-binding polypeptide that is structurally and functionally analogous to calmodulin, an important calcium-binding protein widely distributed in nature. Four molecules of calcium ion are bound per molecule of troponin C or calmodulin, and both molecules have a molecular mass of 17 kDa. 

The calcium mediated contraction of smooth muscle, which unlike striated muscle does not contain troponin, is quite different and requires a particular calcium-binding protein called calmodulin. Calmodulin (CM) is a widely distributed regulatory protein able to bind, with high affinity, four Ca2+ per protein molecule. The calcium—calmodulin (CaCM) complex associates with, and activates, regulatory proteins, usually enzymes, in many different cell types in smooth muscle the target regulatory proteins are caldesmon (CDM) and the enzyme myosin light chain kinase (MLCK). As described below, CaCM impacts on both actin and myosin filaments. 

A protein of similar molecular weight to that of rat oncomodulin, rat and rabbit parvalbumins, S100, and the vitamin D-dependent calcium-binding proteins has been isolated from chicken gizzard smooth muscle. In this case, however, the fluorescence emission from the four tyrosine residues is quenched by Ca2+ binding.(160) The decrease in fluorescence intensity was used to suggest that there are two different classes of Ca2+binding sites. 

Calcium-binding protein, carp muscle (Kretsinger and Nockolds, 1973)... 

S-100 protein (38) is a 20-kDa calcium-binding protein composed of two subunits, S-lOOa and S-IOOP, which are differentially expressed by individual human tissues. For example, S-100(a,a) is found in myocardial and skeletal muscle cells S-100(a,P) is found in glial cells, melanocytes, chondrocytes, and adnexal glands of the skin and S-100(P,P) is found in Schwann cells and Fangerhans cells of the skin (39). There are currently monoclonal antibodies... 

PDB ID 4TNC) This calcium-binding protein associated with muscle has separate calcium-binding domains, indicated in blue and purple. 

A variety of other calcium transport systems are associated with Ca21-activated ATPases. The extraembryonic structure, the chorioallantoic membrane, of the chick embryo is responsible for the translocation of over 120 mg of eggshell calcium into (he embryo during development. The enzyme responsible for this is a (Ca2+, Mg2+)-ATPase with Km values for Ca2+ of 30 p,mol dm-3 and 0.3 mmol dm-3, and a molecular weight of 170 000. The enzyme can be crossiinked and co-isolated with a calcium-binding protein.158 Transport of Ca2+ is also associated with (Ca2+, Mg2+)-ATPases in neutrophil plasma membranes,159 transverse tubule membranes from rabbit skeletal muscle,160 rabbit myocardial membrane,161 endoplasmic reticulum,162 sar-colemma,163 brain microsomes,164 the Golgi apparatus165 and rat liver plasma membranes.166... 

Troponin C from rabbit skeletal and bovine cardiac muscle has a molecular weight of about 18 000. Skeletal TN-C has four sites for Ca2+. Two of these (III and IV) are high affinity sites (K < 107 dm3 mol-1) which also bind Mg2+ competitively, with K = 103 dm3 mol-1. The remaining two (I and II) appear to be specific for Ca2+, although of lower affinity (K 105 dm3 mol-1).234 These two sites are the only sites in calcium-binding proteins that do not bind Mg2+ with constants in the range 102-103 dm3 mol-1. Cardiac TN-C contains two Ca2+-Mg2+ sites, one Ca2+-specific site and one low affinity site for Ca2+, in which the two aspartate residues in the skeletal TN-C protein are replaced by leucine and alanine residues.235... 

---