Calcium-binding domains

Figure 2.19 Organization of polypeptide chains into domains. Small protein molecules like the epidermal growth factor, EGF, comprise only one domain. Others, like the serine proteinase chymotrypsin, are arranged in two domains that are required to form a functional unit (see Chapter 11). Many of the proteins that are involved in blood coagulation and fibrinolysis, such as urokinase, factor IX, and plasminogen, have long polypeptide chains that comprise different combinations of domains homologous to EGF and serine proteinases and, in addition, calcium-binding domains and Kringle domains.

Illarionova, V. A., et al. (1997). Removal of essential ligand in N-terminal calcium-binding domain of obelin does not inactivate the photoprotein or reduce its calcium sensitivity, but dramatically alters the kinetics of the luminescent reaction. In Hastings, J. W., et al. (eds.), Biolu-min. Chemilumin., Proc. Int. Symp., 9th, 1996, pp. 431 —434. Wiley, Chichester, UK. 

R. W. Wallace, E. A. Tallant, M. E. Dockter, and W. Y. Cheung, Calcium binding domains of calmodulin. Sequence of fill as determined by terbium luminescence, J. Biol. Chem. 257, 1845-1854 (1982). 

More recently, workers in Japan published the solution structure of yeast (Saccharomyces cerevisiae) apo-calmodulin (PDB ILKJ). Yeast calmodulin is 60% identical in its amino acid sequence with vertebrate CaMs. The ILKJ N-terminal domain with its two helix-loop-helix calcium-binding domains looks quite similar to those of IDMO and ICFD (see Figure 6.23). 

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

Trichohyalin contains extensive repeat sequence blocks, which are predicted to form an elongated, flexible single-stranded o-helical rod (Lee et al, 1993). These predictions are consistent with biochemical and electron microscopical analysis showing an extended shape with overall dimensions of 85 nm. Similar to profilaggrin, the N-terminus comprises an S-100 protein-like calcium-binding domain. 

Presland, R. B., Haydock, P. V., Fleckman, P., Nirunsuksiri, W., and Dale, B. A. (1992). Characterization of the human epidermal profilaggrin gene. Genomic organization and identification of an S-100-like calcium binding domain at the amino terminus. / Biol. Chem. 267, 23772-23781. 

Gene fusion with calcium-binding domain... 

Fig. 12. Predicted domain structure of the small calcium-binding protein BM-40/os-teonectin/SPARC. Numbering is according to the sequence of SPARC (Mason et al., 1986a), but omits the signal peptide. A dashed line denotes predicted a helix, C identifies cysteine residues, and + indicates clusters of basic residues. A potential calcium-binding domain of the EF type is noted as well as a cluster of glutamic acids. Modified from Engel et al. (1987).

Also, destruction of native conformation by mutation of calcium-binding domains of major carp allergen resulted in reduced IgE reactivity confirmed by skin prick testing. Immunization of mice with the mutated parvalbumin induced IgG antibodies, which inhibited the binding of allergic patient s IgE to wild-type parvalbumin (Swoboda et al. 2007). 

Engel E, Richter K, Obermeyer G, Briza P, Kungl AJ, Simon B, Auer M, Ebner C, Rheinbeiger HJ, Breitenbach M, Ferreira F Immunological and biolc ical properties of Bet v 4, a novel birch pollen allergen with two EF-hand calcium-binding domains. J Biol Chem 1997 272 28630-28637. 

Basani RB, Vilaire O, Shattil SJ, et al. Glanamann thrombasthenia due to a two amino acid deletion in the fourth calcium binding domain of alpha lib Demonstratiem of the importance of calcium binding domains in the conformation of alphallbbeta3. Blood 1996 88 167-173. 

Fig. 3 Glanzmann thrombasthenia mutations within the P-propeller stiucture of GPIIb A schematic drawing of the GPIIb p-propeller structural model showing the P-strands (arrows) and connecting strand arrangements . The propeller is drawn like a cylinder and each blade of the propeller is labeled W1-W7. The P-strands are numbered 1-4 with the first strand located toward the center and bottom and the fourth strand located outside and top of the cylinder. Hie wide ribbons represent the connections between the fourth P-strand of one blade and the first p-strand of the next blade. The ladder-like connections represent the calcium-binding domains and are located on the bottom of the cylinder. The Glanzmann thrombasthenia mutations are represented by black dots and the black bar in W2 represents an intradisulfide bond.

Fig. 4. Glazmann thrombasdienia mutations within the P-propeller sequence for GPIIb The amino-terminal sequence of GPIIb from residues 1-452 that form the seven blades of the p-propeller. The Glanzmann thrombosthenia mutations are shown under the GPIIb sequence and are listed by the patient designations as represented in Table 1. W1-W7 refer to the seven blades and the bold letters designate the amino acids that form the P-strands. The dashed line above the sequence in the second and third P-strand sequence of W2 designates the disulfide bond formed by the two cysteine residues affected by the Arab and patient CW deletion mutations and the italic letter that are underlined by dashes in W4-W7 represent the calcium-binding domains. ...

The adhesion of cells to each other is normally due to interactions that involve a number of proteins of the extracellular matrix and the plasma membrane. Cadherin is a membrane-boimd protein. The N terminus of cadherin is extracellular. The N termini of cadherins sticking out of adjacent cells bind to each other. This interaction requires calcivun ions, hence the name Cadherin. An intracellular interaction is also required for adhesion to occur between cells. The C terminus of cadherin contacts the cytosol and binds to a protein called catenin (pronounced ca-TEE-nin). Catenin, in turn, binds to the cytoskeleton. The cytoskeleton is a network of proteins that crisscross about the plasma membrane and through the cell. Defects in the cadherin gene have been found in many samples of colorectal cancer. These mutations tend to occur in the N-terminal region, i.e., in the extracellular calcium-binding domain. 

Many cells secrete at least one of the three immature forms of TGF-P, and essentially all cells have receptors that respond to the presence of mature TGF-P in the stroma. In the periodontium, TGF-P stimulates fibroblast and osteoblast proliferation during connective tissue or bone remodeling (Sect. 10.1.3), and maintains the proliferation of dentally attached epithelial cells (Sect. 5.2.3). The linker domains that connect calcium binding domains in fibrillin are identical to the sequence of protein receptors that bind to TGF-P (Sect. 6.1.1). 

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