Calcium ions and proteins

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

In addition to 1-a-hydroxylase, the kidney also possesses a 24-hydroxylase which uses calcidiol as substrate the product of the reaction, 24,25 dihydroxy D3, is biologically inactive. This represents an important control point in the pathway. The activity of the 1-a-hydroxylase is promoted by calcium ions and the action of PTH acting via a G-protein/cAMP cascade. However, calcitriol itself simultaneously induces the 24-hydroxylase and suppresses 1-a-hydroxylase creating an effective feedback loop (Figure 8.12). 

This group or complex of proteins may be isolated from cold-staUe microtubules. Their ability to stabilize microtubules appears to be diminished by the comUned action of calcium ion and calmodulin (Job et al., 1983). The role in controlling or affecting microtubule stability at physiological temperatures remains to be established... 

This enzyme [EC 2.7.1.123], also referred to as calcium/ calmodulin-dependent protein kinase type II, and micro-tubule-associated protein MAP2 kinase, catalyzes the reaction of ATP with a protein to produce ADP and an 0-phosphoprotein. The enzyme requires calcium ions and calmodulin. Proteins that can serve as substrates include vimentin, synapsin, glycogen synthase, the myosin light-chains, and the microtubule-associated tau protein. This enzyme is distinct from myosin light-chain kinase [EC 2.7.1.117], caldesmon kinase [EC 2.7.1.120], and tau-protein kinase [EC 2.7.1.135]. 

An analysis of metal binding to peptide carbonyl groups (Chakrabarti, 1990), mainly calcium ions in protein crystal structures, shows that the cations tend to lie in the peptide plane near the C=0 bond direction. Generally, this binding occurs in turns in proteins or in regions with no regular secondary structures. Ca---0 distances range from 2.2 to 2.5 A, and metal ions do not deviate by more than 35° from the peptide plane. Thus, metal ions in proteins do not, Chakrabarti observed, bind in lone-pair directions. 

A key to the development of osteoblasts appears to be an osteoblast-specific transcription factor OS/2 or Cbfal.693-695 Mutations in human Cbfal are linked to a series of skeletal defects.696 A unique change accompanying conversion of a precursor cell into an osteoblast is the formation of a 49-residue y-carboxyglutamate (Gla)-containing protein called osteocalcin.697 (See also Box 15-F). It is the most abundant noncollagenous protein of bone. Its three Gla residues doubtless help to bind calcium ions and osteocalcin may be an initiator of crystallization. Osteocalcin has also been found in fish scales.698 Also present in bone is a 74-residue matrix Gla protein which has 5 Gla residues.699... 

Protein sequence and structure of troponin (TN-C) and carp muscle calcium binding parvalbumin (MCBP) are known199-201). MCBP has two calcium binding regions each consisting of an a-helix, a loop about the calcium ion and another a-helix, as so-called EF hand (Fig. 21)202,203). 

Fig. 11. Binding of calmodulin to an array of a diverse set of 144 human proteins enables novel, calcium-dependent interactions to be identified. (A) Binding of Cy3-labeled anti-His tag antibody to the array allows the relative amount of protein in each spot to be determined. (B) Binding of Cy3-labeled calmodulin allows potential interacting partners to be identified. (C) Histogram showing the relative amount of calmodulin bound per unit protein in the presence of calcium ions. (D) Histogram showing the relative amount of calmodulin bound per unit protein in the presence of calcium ions and a high concentration of a divalent metal ion chelator, ethylenediamine tetra-acetic acid.

Protein Composition of Milk. Skim milk is a colloidal suspension of extreme complexity. The particulate phase, the casein micelles, consists primarily of a mixture of asi, as2, / , and x-caseins combined with calcium ions and an amorphous calcium-phosphate-citrate complex. The soluble phase contains lactose, a fraction of the caseins and calcium, and, in raw milk, the whey proteins, which are predominantly /3-lacto-globulin and a-lactalbumin. When milk is centrifuged at high speed (in our experiments, 30 min at 110,000 X gravity), the casein micelles sediment. This permits one to separate the two physical phases of skim milk and to measure changes in composition of the phases resulting from... 

Fig. 17.6. The vectorial pumping of calcium ions and protons across the mitochondrion membranes. A schematic enlargement of the inner (cristae) membrane is shown to indicate the existence of protein-based electron (e ) and proton (H+) conduction pathways (from Ref. 26 with permission).

---