Calmodulin characteristics

Fig. 9. The interaction of ACTH with the cyclic AMP and calcium intracellular messenger systems in the regulation of steroidogenesis in the adrenocortical zona glomerulosa cell comparison with angiotensin II and potassium. ACTH activates both adenylate cyclase and calcium influx, here shown as involving two receptor subtypes (R, and R2) although such receptor subtypes have not been identified. The A-kinase and calmodulin systems produce individual responses of characteristic amplitudes and time-courses, which combine to give the observed response of the intact cell. The sequence of events for ACTH is compared to those for the other two major stimuli of steroidogenesis in the zona glomerulosa cell, angiotensin II and potassium. From Ref. 41.

The lanthanides form a series of ions of closely related size and bonding characteristics and in many respects resemble Ca +, for which they often substitute isomorphously in biological systems. Since different Ln ions can be probed with particular spectroscopic techniques (e.g. Eu + and Tb +, fluorescence Gd +, ESR Nd +, electronic spectra), in favourable circumstances it should be possible to obtain information about the binding site of spectroscopically inactive Ca + in several ways. Systems smdied include the calciumbinding sites in calmodulin, trypsin, parvalbumin, and the Satellite tobacco necrosis virus. 

As was pointed out above, inside the cell Ca levels are not usually transmitted directly to targets, but are first processed by sensor proteins. Many of them, like calmodulin (described later), bind Ca to characteristic EF-hand motifs undergoing in the process a conformational change, which is a prerequisite for their subsequent interaction with their respective target enzymes. However, some of these Ca sensors, like protein kinase C, calpains, and calcineurin, are themselves Ca -sensitive enzymes, while others like gelsolin and the annexins do not contain EF hands. 

The most widespread Ca2+ receptor is calmodulin. Calmodulin is a small protein of ca. 150 amino acids (review Hoeflich and Ikura, 2002). The structure of the Ca2+/calmo-dulin complex has two globular domains that are separated by a long a-helical section (Fig. 6.13a). Both globular domains have two binding sites for Ca2+. Ca2+ is bound via a characteristic helix-loop-helix structure, also known as an EF structure. Similar EF structures are found in many, but not all, Ca2+-binding proteins. The binding affinity... 

The activity of plasma-membrane Ca ATPases is regulated by calmodulin, a cytosolic Ca -binding protein (see Figure 3-28). A rise in cytosolic Ca induces the binding of Ca ions to calmodulin, which triggers allosteric activation of the Ca ATPase. As a result, the export of Ca ions from the cell accelerates, quickly restoring the low concentration of free cytosolic Ca characteristic of the resting cell. 

Schematic structure of the calmodulin (CaM)-activated plasma membrane Ca -ATPase of erythrocytes. Some molecular characteristics are = 138,000 transport rate (30°C), 20-70 Ca " ions per protein molecule per second KMlCa " ) = 0.5 /u,M (cytoplasmic side in high-affinity form) Ca /ATP ratio, 1( ) activated not only by CaM but also by acidic phospholipids and unsaturated fatty acids. Figure kindly provided by R. Moser and E. Carafoli.

Gross, S. S., Jaffe, E. A., Levi, R., and Kilbourn, R. G. (1991). Cytokine-activated endothelial cells express an isotype of nitric oxide synthase which is tetrahydrobiopterin-dependent, calmodulin-independent and inhibited by arginine analogs with a rank-order of potency characteristic of activated macrophages. Biochem. Biophys. Res. Commun. 187,823-829. Gryglewski, R. J., Bolting, R., and Vane, J. R. Mediators producted by tbe endothelial cell. Hypertension 12, 530-548. 

---