Abstract
Calcium plays an important role in many biological processes. At first, it might seem that the most important role of calcium in biology is a structural one, and indeed it may be argued that this is true. Hydroxyapatite, a co-crystal of calcium, phosphate, and hydroxide ions, forms the matrix of tooth enamel, the hardest substance in the human body. Calcium phosphate is also responsible for the rigidity of bone, and the deposition of this matrix in bone is a very tightly controlled biological process (1). In fact, the vast majority of calcium (more than 99%) is immobilized in bones and teeth in humans. Poor diet or improper regulation of calcium deposition can lead to diseases such as childhood rickets or osteoporosis in older adults. Moreover, calcium is also important structurally in other organisms; for example, calcium carbonate is the major component of egg shells and also of the exoskeleton of animals such as mollusks and barnacles. Nutritionally, calcium is found in many foods, but of course the major source in most human diets is dairy products. In milk, a predominant class of proteins is the caseins, which function to solubulize calcium phosphate microgranules by surrounding them in a micellar structure (2), providing an important mineral nutrient in liquid form.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bronner, F. and Petpulik, M. (1992) Extra-and intracellular calcium and phosphate regulation in: Basic Research to Clinical Medicine, CRC Press, Boca Raton, Florida.
Holt, C. (1992) Structure and stability of bovine casein micelles. Adv. Protein Chem. 43, 63–151.
Nelsestuen, G. L. and Gaul Ostrowski, B. (1999) Membrane association with multiple calcium ions: vitamin-K-dependent proteins, annexins and pentraxins. Curr. Opin. Struct. Biol. 9, 433–437.
Sunnerhagen, M., Forsén, S., Hofren, A. M., Drakenberg, T., Teleman, O., and Stenflo, J. (1995) Structure of the Ca2+-free Gla domain sheds light on membrane binding of blood coagulation proteins. Nat. Struct. Biol. 2, 504–509. Erratum (1996) Nat. Struct. Biol. 3,103.
Selander-Sunnerhagen, M., Ullner, M., Persson, E., Teleman, O., Stenflo, J., and Drakenberg, T. (1992) How an epidermal growth factor (EGF)-like domain binds calcium. High resolution NMR structure of the calcium form of the NH2-terminal EGF-like domain in coagulation factor X. J. Biol. Chem. 267, 19,642–19,649.
Maurer, P., E., and Engel, J. (1996) Extracellular calcium-binding proteins. Curr. Opin. Cell Biol. 8, 609–617.
Downing, A. K., Knott, V., Werner, J. M., Cardy, C. M., Campbell, I. D., and Handford, P. A. (1996) Solution structure of a pair of calcium-binding epidermal growth factor-like domains: implications for the Marfan syndrome and other genetic disorders. Cell 85, 597–605.
Muranyi, A., Finn, B. E., Gippert, G. P., Forsen, S., Stenflo, J., and Drakenberg, T. (1998) Solution structure of the N-terminal domain from human factor VII. Biochemistry 37, 10,605–10,615.
McKenzie, H. A. and White, F. H., Jr. (1991) Lysozyme and α-lactalbumin: struc-ture, function, and interrelationships. Adv. Protein Chem. 41, 173–315.
Aramini, J. M., Drakenberg, T., Hiraoki, T., Ke,Y., K., and Vogel, H. J. (1992) Calcium-43 NMR studies of calcium-binding lysozymes and α-lactalbumins. Biochemistry 31, 6761–6768.
Aramini, J. M., Hiraoki, T., Nitta, K., and Vogel, H. J. (1995) Admium-113 NMR studies of metal ion binding to bovine and human a-lactalbumin and equine lysozyme. J. Biochem. 117, 623–238.
Pan, C. Q. and Lazarus, R. A. (1999) Ca2+-dependent activity of human DNase I and its hyperactive variants. Protein Sci. 8, 1780–1788.
Smith, C. A., Toogood, H. S., Baker, H. M., Daniel, R. M., and Baker, E. N. (1999) Calcium-mediated thermostability in the subtilisin superfamily: the crys-tal structure of Bacillus Ak. 1 protease at 1.8 Å resolution. J. Mol. Biol. 294, 1027–1040.
Hosfield, C. M., Elce, J. S., Davies, P. L., and Jia, Z. (1999) Crystal structure of calpain reveals the structural basis for Ca2+-dependent protease activity and a novel mode of enzyme activation. EMBO J. 24, 6880–6889.
Strobl, S., Fernandez-Catalan, C., Braun, M., Huber, R., Masumoto, H., Nakagawa, K., Irie, A., Sorimachi, H., Bourenkow, G., Bartunik, H., Suzuki, K., and Bode, W. (2000) The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium. Proc. Natl. Acad. Sci. USA 97, 588–592.
Yin, H. L. and Stossel, T. P. (1980) Purification and structural properties of gelsolin, a Ca2+-activated regulatory protein of macrophages. J. Biol. Chem. 255, 9490–9493.
Nunnally, M. H., Powell, L. D., and Craig, S. W. (1981) Reconstitution and regula-tion of actin gel-sol transformation with purified filamin and villin. J. Biol. Chem. 256, 2083–2086.
Maekawa, S. and Sakai, H. (1990) Inhibition of actin regulatory activity of the 74-kDa protein from bovine adrenal medulla (adseverin) by some phospholipids. J. Biol. Chem. 265, 10,940–10,942.
Yin, H. L. and Stossel, T. P. (1979) Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature 281, 583–586.
Burtnick, L. D., Koepf, E. K., Grimes, J., Jones, E. Y., Stuart, D. I., McLaughlin, P. J., and Robinson, R. C. (1997) The crystal structure of plasma gelsolin: implications for actin severing, capping, and nucleation. Cell 90, 661–670.
Robinson, R. C., Mejillano, M., Le, V. P., Burtnick, L. D., Yin, H. L., and Choe, S. (1999) Domain movement in gelsolin: a calcium-activated switch. Science 286, 1939–1942.
Vogel, H. J. (1994) Calmodulin: a versatile calcium mediator protein. Biochem. Cell Biol. 72, 357–376.
Means, A. R., VanBerkum, M. F. A., Bagchi, I., Lu, K. P., and Rasmussen, C. D. (1991) Regulatory functions of calmodulin. Pharmac. Ther. 50, 255–270.
Williams, R. J. P. (1992) Calcium fluxes in cells: new view on their significance. Cell Calcium 20, 87–93.
Fraústo da Silva, J. J. R. and Williams, R. J. P. (1991) The Biological Chemistry of the Elements. Oxford University Press, Toronto.
Lippard, S. J. and Berg, J. M (1994) Principles of Bioinorganic Chemistry. Univer-sity Science Books, Mill Valley, CA.
Dubois, T., Oudinet, J. P., Mira, J. P., and Russo-Marie, F. (1996) Annexins and protein kinases C. Biochim. Biophys. Acta 1313, 290–294.
Nalepski, E. A. and Falke, J. J. (1996) The C2 domain calcium-binding motif: struc-tural and functional diversity. Protein Sci. 5, 2375–2390.
Rizo, J. and Südhof, T. C. (1998) C2-domains, structure and function of auniversal Ca2+-binding domain. J. Biol. Chem. 273, 15,879–15,0882.
Strynadka, N. C. J. and James, M. N. G. (1989) Structures of the helix-loop-helix calcium binding proteins. Annu. Rev. Biochem. 58, 951–998.
Ikura, M. (1996) Calcium binding and conformational response in EF-hand proteins. Trends Biochem. Sci. 21, 14–17.
Kawasaki, H., Nakayama, S., and Kretsinger, R. H. (1998) Classification and evolution of EF-hand proteins. Biometals 11, 277–295.
Kretsinger, R. H. and Nockolds, C. E. (1973) Carp muscle calcium-binding protein II. Structure determination and general description. J. Biol. Chem. 248, 3313–3326.
Vijay-Kumar, S., and Cook, W. J. (1992) Structure of a sarcoplasmic calcium-bind-ing protein from Nereis diversicolor refined at 2.0 Å resolution. J. Mol. Biol. 224, 413–426.
Tanaka, T., Ames, J. B., Harvey, T. S., Stryer, L., and Ikura, M. (1995) Sequestration of the membrane-targeting myristoyl group of recoverin in the calcium-free state. Nature 376, 444–447
Smith, S. P. and Shaw, G. S. (1998) A change in hand mechanism for S100 signalling. Biochem. Cell Biol. 76, 324–333.
Heizmann, C. W. and Cox, J. A. (1998) New perspectives on S100 proteins: a multifunctional Ca2+-, Zn2+-, and Cu2+-binding protein family. Biometals 11, 383–397.
Donato, R. (1999) Functional roles of S100 proteins, calcium binding proteins of the EF-hand type. Biochim. Biophys. Acta 1450, 191–231.
Haeseleer, F., Sokal, I., Verlinde, C. L. M., Erdjument-Bromage, H., Tempst, P., Pronin, A. N., et al. (2000) Five members of a novel Ca2+-binding protein (CABP) subfamily with similarity to calmodulin. J. Biol. Chem. 275, 1247–1260.
Méhul, B., Bernard, D., Simonetti, L., Bernard, M. A., and Schmidt, R. (2000) Identification and cloning of a new calmodulin-like protein from human epidermis. J. Biol. Chem. 275, 12,841–12,847.
Farah, C. S. and Reinach, F. C. (1995) The troponin complex and regulation of muscle contraction. FASEB J. 9, 755–767.
Gagné, S. M., Li, M. X., McKay, R. T., and Sykes, B. D. (1998) The NMR angle on troponin C. Biochem. Cell Biol. 76, 302–312.
Filatov, V. L., Katrukha, A. G., Bulargina, T. V., and Gusev, N. B. (1999) Troponin: structure, properties, and mechanism of functioning. Biochemistry (Moscow) 64, 1155–1174 (translated from Russian).
Zhang, M. and Yuan, T. (1998) Molecular mechanisms of calmodulin’s functional versatility. Biochem. Cell Biol. 76, 313–323.
Crivici, A. and Ikura, M. (1995) Molecular and structural basis of target recognition by calmodulin. Annu. Rev. Biophys. Biomol. Struct. 24, 85–116.
Babu, Y. S., Bugg, C. E., and Cook, W. J. (1988) Structure of calmodulin refined at 2.2 Å resolution. J. Mol. Biol. 204, 191–204.
Chattopadhyaya, R., Meador, W. E., and Means, A. R. (1992) Calmodulin structure refined at 1.7 Å resolution. J. Mol. Biol. 228, 1177–1192.
Heidorn, D. B. and Trewhella, J. (1988) Comparison of the crystal and solution structures of calmodulin and troponin C. Biochemistry 27, 909–915.
Ikura. M., Spera, S., Barbato G., Kay L.E., Krinks M., and Bax, A. (1991) Secondary structure and side-chain 1H and 13C resonance assignments of calmodulin in solution by heteronuclear multidimensional NMR spectroscopy. Biochemistry 30, 9216–9228.
Barbato, G., Ikura, M., Kay, L. E., Pastor, R. W., and Bax, A. (1992) Backbone dynamics of calmodulin studied by 15N inverse detected two-dimensional NMR spectroscopy: the central helix is flexible. Biochemistry 31, 5269–5278.
Strynadka, N. C. J. and James, M. N. G. (1989) Structures of the helix-loop-helix calcium binding proteins. Annu. Rev. Biochem. 58, 951–998.
Marsden, B. J., Shaw, G. S., and Sykes, B. D. (1990) Calcium binding proteins. Elucidating the contributions to calcium affinity from an analysis of species variants and peptide fragments. Biochem. Cell Biol. 68, 587–601.
Reid, R. E., Gariépy, J., Saund, A. K., and Hodges, R. S. (1981) Calcium-induced protein folding. Structure-affinity relationships in synthetic analogs of the helix-loop-helix calcium binding unit. J. Biol. Chem. 256, 2742–2751.
Gariépy, J., Sykes, B. D., Reid, R. E., and Hodges, R. S. (1982) Proton nuclear magnetic resonance investigation of synthetic calcium binding peptides. Biochemistry 21, 1506–1512.
Andersson A., Forsén, S., Thulin, E., and Vogel, H. J. (1983a) Cadmium-113 nuclear magnetic resonance studies of proteolytic fragments of calmodulin: assignment of strong and weak cation binding sites. Biochemistry 22, 2309–2313.
Brokx, R., D. and Vogel, H. J. (2000) Peptide and metal ion dependent association of isolated helix-loop-helix calcium binding domains: studies of thrombic fragments of calmodulin. Protein Set 9, 964–975.
Kuboniwa, H., Tjandra, N., Grzesiek, S., Ren, H., Klee, C. B., and Bax, A. (1995) Solution structure of calcium-free calmodulin. Nat. Struct. Biol. 2, 768–776.
Zhang, M., Tanaka, T., and Ikura, M. (1995) Calcium-induced conformational transition revealed by the solution structure of apo calmodulin. Nat. Struct. Biol. 2, 758–762.
Rhoads, A. R. and Friedberg, F. (1997) Sequence motifs for calmodulin recognition. FASEB J. 11, 331–340.
Zhang, M. and Vogel, H. J. (1997) Interaction of a partial calmodulin-binding domain of caldesmon with calmodulin. Prot. Pept. Lett. 4, 291–297.
Yuan T. and Vogel H. J. (1998) Calcium-calmodulin-induced dimerization of the carboxyl-terminal domain from petunia glutamate decarboxylase. A novel calmodulin-peptide interaction motif. J. Biol. Chem. 273, 30,328–30,335.
Ikura, M., Clore, M., Gronenborn, A. M., Zhu, G., Klee, C. B., and Bax, A. (1992) Solution structure of a calmodulin-target peptide complex by multidimensional NMR. Science 256, 632–638.
Meador, W. E., Means, A. R., and Quiocho, F. A. (1992) Target enzyme recognition by calmodulin: 2.4 Å structure of a calmodulin-peptide complex. Science 257, 1251–1255.
Meador, W. E., Means, A. R., and Quiocho, F. A. (1993) Modulation of calmodulin plasticity in molecular recognition on the basis of X-ray structures. Science 262, 1718–1721.
Elshorst, B., Hennig, M., Forsterling, H., Diener, A., Maurer, M., Schulte, P., et al. (1999) NMR solution structure of a complex of calmodulin with a binding peptide of the Ca2+pump. Biochemistry 38, 12,320–12,332.
Osawa, M., Tokomitsu, H., Swindells, M. B., Kurihara, H., Orita, M., Shibanuma, T., et al. (1999) A novel calmodulin target recognition revealed by its NMR structure in complex with a peptide derived from Ca2+-calmodulin dependent protein kinase kinase. Nat. Struct. Biol. 6, 819–824.
Vogel, H. J. and Zhang, M. (1995) Protein engineering and NMR studies of calmodulin Mol. Cell Biochem. 149-150, 3–15.
Yuan, T., Ouyang, H., and Vogel, H. J. (1999) Surface exposure of the methionine side chains of calmodulin in solution. J. Biol. Chem. 274, 8411–8420.
Goldberg, J., Nairn, A. C., and Kuriyan, J. (1996) Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I. Cell 84, 875–887.
Koradi, R., Billeter, M., and Wuthrich, K. (1996) MOLMOL: a program for display and analysis of macromolecular structures. J. Mol. Graphics 14, 29–32.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc.
About this protocol
Cite this protocol
Vogel, H.J., Brokx, R.D., Ouyang, H. (2002). Calcium-Binding Proteins. In: Vogel, H.J. (eds) Calcium-Binding Protein Protocols. Methods in Molecular Biology™, vol 172. Humana Press. https://doi.org/10.1385/1-59259-183-3:003
Download citation
DOI: https://doi.org/10.1385/1-59259-183-3:003
Publisher Name: Humana Press
Print ISBN: 978-0-89603-688-8
Online ISBN: 978-1-59259-183-1
eBook Packages: Springer Protocols