Calbindin structure

Parvalbumins, which are also found in other vertebrates, are high-affinity Ca2+-buffers." Additional calcium buffers with EF-hand structures are the vitamin D-induced calbindins. One 9-kDa calbindin is found in mammalian intestinal tissue and in skin. It has two helix-loop-helix Ca2+-binding sites of differing affinity101102 that presumably function in the absorption of calcium. A 28-kDa vitamin D-dependent protein from chicken intestine contains six similar Ca2 +-binding loops.97 103... 

Analogously, the pseudocontact shifts were used to refine the solution structure of the Ce(III), Dy(III) and Yb(III) derivatives of monolanthanide-substituted Calbindin D9k. Since the three lanthanides span a wide range of magnetic anisotropies, the refinement was effective in shells from the metal of 5—15 A for Ce(III), 9-25 A for Yb(III), 13-40 A for Dy(III), as useful pseudocontact shifts were observed in these shells (Fig. 5.59) [167]. Therefore, by using different lanthanides it was possible to enlighten shells at variable distances from the metal itself. 

In the rat, the dorsal tier includes cells of the dorsal parts of the VTA and SNc and cells of the RRA innervating the limbic portion of the striatum and limbic cortical fields, as well as the ventral basal forebrain structures, such as the olfactory tubercle and the amygdala. Neurons of the dorsal tier are mostly fusiform, with dendrites oriented horizontally in the mediolateral plane of the SNc. From the neurochemical point of view, neurons of the dorsal tier contain relatively low levels of TH mRNA and dopamine transporter (DAT) mRNA, and the calcium binding protein calbindin is colocalized with DA in most dorsal tier neurons (Gerfen, 1985) (Figs. 4D 13C,D). 

The ventral tier includes in the rat cells of the ventral parts of the VTA and SNc which innervate the neostriatum and dorsal structures of the basal forebrain such as the septum. Ventral tier neurons include the columns of dopaminergic neurons which pierce the SNr and project to the striatum (Figs. 12, 13A). The ventral tier neurons express high levels of DAT mRNA and do not exhibit calbindin immunoreactivity (Gerfen, 1985). 

The E-F hand proteins parvalbumin, troponin C, calmodulin, calbindin and onco-modulin have been studied with respect to lanthanide interactions. The crystal structure of parvalbumin [82] consists of six a-helical regions labeled as A-F. One Ca2+ ion is bound in the loop joining C and D helices and the second ion in the loop of E-F. Calcium ion is bound to six protein ligands in the CD site. Ca2+ in the EF site is bound to seven protein ligands and a water molecule. 

In native proteins of known three-dimensional structure about 7% of all prolyl peptide bonds are cis (Stewart et al., 1990 MacArthur and Thornton, 1991). Usually, the conformational state of each peptide bond is clearly defined. It is either cis or trans in every molecule, depending on the structural framework imposed by the folded protein chain. There are a few exceptions to this rule. In the native states of staphylococcal nuclease (Evans et al., 1987), insulin (Higgins et al., 1988), and calbindin (Chazin et al., 1989) cis-trans equilibria at particular Xaa-Pro bonds have been detected in solution by NMR. In staphylococcal nuclease, the cis conformer of the Lys 116-Pro 117 bond can be selectively stabilized by bind-... 

Kosaka K, Aika Y, Toida K, Kosaka T 2001. Structure of intraglomerular dendritic tufts of mitral cells and their contacts with olfactory nerve terminals and calbindin-immunoreactive type 2 perigiomeruiar neurons. J Comp Neurol 440 219-235. 

Ohm TG, Muller H, Braak E. 1991. Calbindin-D-28k-like immunoreactive structures in the olfactory bulb and anterior olfactory nucleus of the human adult Distribution and cell typology-partial complementarity with parvalbumin. Neuroscience 42 823-840. 

Children are particularly vulnerable to excess strontium because the immature skeleton has a high rate of bone remodeling, and strontium adversely affects bone development in several ways, as demonstrated in animal studies. In chickens and rats, excess strontium suppresses the activation of vitamin D3 in the kidney, which severely reduces the expression of calbindin D mRNA and the translation of calbindin D protein in the duodenum (Armbrecht et al. 1979, 1998 Omdahl and DeLuca 1972). As a result, duodenal absorption of calcium is reduced. Strontium also binds directly to hydroxyapatite crystals, which may interfere with the normal crystalline structure of bone in rats (Storey 1961). In addition, excess strontium may prevent the normal maturation of chondrocytes in the epiphyseal plates of long bones of rats (Matsumoto 1976). Excess strontium apparently interferes with the mineralization of complexed acidic phospholipids that is thought to help initiate the formation of hydroxyapatite crystals in developing bone (Neufeld and Boskey 1994). As a result, affected bone contains an excess of complexed acidic... 

In crystal structures of folded proteins the prolyl peptide bonds are generally either cis or trans in every molecule. There is, however, an increasing number of exceptions to this rule, and cis/trans equilibria have been found, in particular by 2D-NMR spectroscopy in solution. Examples include staphylococcal nuclease (Evans et al, 1987), insulin (Higgins etal., 1988), calbindin (Chazin et al., 1989 Kordel et al., 1990), scorpion venom Lqh-8/6 (Adjadj et al., 1997), human interleukin-3 (Feng et al., 1997), and the TB6 domain of human fibrillin-1 (Yuan etal., 1997 Yuan et al., 1998). 

Calbindin Dq M — 8.7 kDa) is another intracellular Ca -binding protein with unknown function. It was briefly mentioned in connection with Ca uptake and transport in the intestine and placenta (Section IV.A). Like the avian calbindin D2Sk, the Dgk calbindin has been observed in many types of tissue. The homology between the Dgk and D2Sk calbindins is much less than the name suggests both their syntheses are, however, regulated by vitamin D. The x-ray stmcture of bovine calbindin Dgk has been determined and refined to a resolution of 2.3 A, and a three-dimensional solution structure of porcine calbindin... 

A surprising discovery about the structure of bovine calbindin D9k in solution has also been made recently. Detailed analysis of the 2D H NMR spectrum of wild-type calbindin has revealed that it exists as a 3 1 equilibrium mixture of two forms, corresponding to a trans and cis conformation around the Gly-42-Pro-43 peptide bond. The global fold appears essentially the same in the two forms, and structural differences are primarily located in the inter-domain loop in which Pro-43 is located. 

The backbone trace of the solution structure of porcine calbindin D9t calculated from NMR data shown in two different views. The position of the calcium ions (blue spheres) is modeled after the crystal structure of bovine calbindin Dg. Figure kindly provided by M. Pique, M. Akke, and W. J. Chazin. 

In the case of the buffering proteins, calcium binding has little or no significant effect on the structure of the protein and the function of the protein is most likely limited to its calcium-binding role. The best studied example of the latter is calbindin D9k. 

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