Calmodulin domain-containing protein

Upon binding calcium ions, the small acidic protein known as calmodulin can activate enzymes by binding to a wide variety of proteins containing cahnodulin-binding domains. Such proteins include cAMP phosphodiesterase, calmodulin-dependent nitric oxide synthase, calmodulin kinases, the plasma membrane calcium pump, calcineurin, and calmodulin-dependent inositol-(l,4,5)-trisphosphate 3-kinase. See also Activation Autoinhibition... 

Domain IV is the C-terminal portion of the protein, and is also known as the calmodulin-like domain due to its similarity with calmodulin. It contains five EF-hand Ca2+-binding motifs, the fifth of which does not bind calcium but is involved in the dimerization with the small subunit, through the interaction with the analogous EF-hand motif in domain VI. The small subunit is composed of two domains (V and VI) separated by a region containing a proline-rich stretch. 

It has been shown that the activity of NO synthases is regulated by cofactors calcium binding protein calmodulin and tetrahydrobiopterin (H4B). Abu-Soud et al. [149] have studied the effect of H4B on the activity of neuronal nNOS I, using the isolated heme-containing oxygenase domain nNOSoxy. It was found that nNOSoxy rapidly formed an oxygenated complex in the reaction with dioxygen, which dissociated to produce superoxide (Reaction (6)) ... 

Synaptobrevins (VAMPs) Synaptogyrin Synaptophysins PKA but diverge C-terminally. Synapsins Ia/b contain C-terminal phosphorylation sites for CaMKII and CDK 5. Interact with microfilaments, neurofilaments, microtubules, SH3 domains, calmodulin and annexin VI in vitro. Small-membrane proteins that are cleaved by tetanus toxin and by botulinum toxins B, D, F and G. Polytopic membrane protein that is tyrosine-phosphorylated. Function unknown. Polytopic membrane proteins, including synaptoporin, that are tyrosine-phosphorylated and bind to synaptobrevins. May regulate SNARE function... 

FIGURE 21-6 Schematic illustration of the overall structure and regulatory sites of eleven different phosphodiesterase subtypes. The catalytic domain of the phosphodiesterases are relatively conserved, and the preferred substrate(s) for each type is shown. The regulatory domains are more variable and contain the sites for binding of Ca2+/calmodulin (CaM) and cGMP, as well as GAF and PAS domains. The regulatory domains also contain sites of phosphorylation by cAMP-dependent protein kinase (PKA). 

The fluorescence of the two tyrosine residues in bovine testes calmodulin was investigated by Pundak and Roche.(123) Upon excitation at 278 nm, a second emission, in addition to tyrosine fluorescence, was observed at 330-355 nm, which they characterized as being due to tyrosinate fluorescence. The tyrosinate fluorescence appeared to be from Tyr-99, which has an anomalously low pKa of about 7 for the phenol side chain. Pundak and Roche(123) reasoned that since tyrosinate emission is apparently not being seen in other species of calmodulin, it is possible that the bovine protein contains a carboxylate side chain in domain III which is amidated in other species. They further argued that the tyrosinate emission from bovine testes calmodulin arises from direct excitation of an ionized tyrosine residue. This tyrosinate fluorescence is discussed in more detail in Section 1.5.2. 

The Ca2+-dependent neutral proteases called calpains are found within the cells of higher animals. The 705-residue multidomain peptide chain of a chicken calpain contains a papain-like domain as well as a calmodulin-like domain.328 It presumably arose from fusion of the genes of these proteins. At least six calpains with similar properties are known.329 Some have a preference for myofibrillar proteins or neurofilaments.330 They presumably function in normal turnover of these proteins and may play a role in numerous calcium-activated cellular processes.331-3323... 

---