Sandbox 4465

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Revision as of 04:21, 17 November 2015

Calmodulin

Calcium is an essential mineral that is needed in the human diet for proper functioning of neurons to strong bones and can also act as a second messenger for enzymes and proteins. Calmodulin (CaM), short for calcium modulated protein, is a small calcium binding protein with a three dimensional structure. Calmodulin has been known to be involved in various Ca2+ - dependent signal transduction pathways, can act as a Ca2+ sensor, and has been involved with regulated protein-kinases.

Its’ importance can be exemplified by the fact that the protein has been known to be highly conserved in eukaryotes. Highly conserved structures that do not undergo significant evolutionary changes imply that the structure is mandatory for cell or organism survival and that any mutations in the genetic sequence that codes for the protein would be deleterious. The function of calmodulin is typically studied using yeast as a model organism. This is done for a variety of reasons, including the fact that yeast has a fully annotated genome with human homologues for genes associated with their ion channels, yeast is fast

Calmodulin in the body

Calmodulin is located and used ubiquitously, but is especially prevalent in brain and muscle tissue. Calmodulin in the cell is mainly localized in organelles and binds to Calcium which then promotes the phosphorylation of protein kinases and activation of other proteins to begin signal transduction for a variety of different pathways, mainly different forms of cell signaling. The phosphorylation of these protein-kinases occurs when Ca2+ reach about 1000 nM and initiates a rapid signaling pathway.

Structural Highlights

Calmodulin has a molecular mass of 16 kilodaltons (kD) and it functions along with ryanodine receptor (RyR). CaM consists of 148 amino acid residues that is characterized by a helix-loop-helix binding motif, also known as the EF hand. Calmodulin has one subunit with a distinct dumbbell shape in which a linker region joins two globular domains. Calmodulin is known to undergo a conformational change upon binding with a calcium ion in which each lobe transitions from a closed conformation to an open conformation. Calmodulin typically wraps around its target, with the two globular domains gripping either side of it. NMR studies clearly show that the connector between the two calcium binding globular domains is flexible even when it is not bound to its target proteins. However, the full range of flexibility can be seen in calmodulin interactions with its target proteins.

Function

Each end of the globular domains of CaM binds to two Calcium ions, which allows CaM to bind to a total of four Calcium ions. The conformational changes which CaM undergoes allow it to be able to bind more specifically. Calmodulin elicits a pathway signal transduction by activating protein kinases which can then go on to phosphorylate other proteins, or other proteins can directly bind to Calmodulin. This would require that the other proteins have a specific binding motif or substrate binding mechanism for Calmodulin. Because there are many different types of binding motifs used by other proteins to interact with Calmodulin, there are no conserved amino acid sequences for CaM binding.

References

Berridge, M. J., Lipp, P., & Bootman, M. D. (2000). The versatility and universality of calcium signalling. Nature Reviews Molecular Cell Biology, 1(1), 11-21. doi:10.1038/35036035

Chan, K. F., & Chen, W. H. (1990). High performance capillary electrophoresis of calmodulin. Electrophoresis, 11(1), 15-18. doi:10.1002/elps.1150110104 [doi]

Eldik, L., & Watterson, D. (1998). Calmodulin and signal transduction. San Diego: Academic Press.

Huang, X., Liu, Y., Wang, R., Zhong, X., Liu, Y., Koop, A., Liu, Z. (2013). Two potential calmodulin-binding sequences in the ryanodine receptor contribute to a mobile, intra-subunit calmodulin-binding domain. Journal of Cell Science, 126(19), 4527–4535.

Joseph, J. D., & Means, A. R. (2002). Calcium Binding Is Required for Calmodulin Function in Aspergillus nidulans. Eukaryotic Cell, 1(1), 119–125. http://doi.org/10.1128/EC.01.1.119-125.2002

Lai, M., Brun, D., Edelstein, S. J., & Novere, N. L. (2015). Modulation of Calmodulin lobes by different targets: An allosteric model with hemi concerted conformational transitions. PLOS Computational Biology. http://doi:10.1371/journal.pcbi.1004063

Lukas, T. J., Haiech, J., Lau, W., Craig, T. A., Zimmer, W. E., Shattuck, R. L., et al. (1988). Calmodulin and calmodulin-regulated protein kinases as transducers of intracellular calcium signals. Cold Spring Harbor Symposia on Quantitative Biology, 53 Pt 1, 185-193.

MacNeil S., Dawson RA., Crocker G., Barton CH., Hanford L., McGurk MR., and Munro DS.,(1988). Extracellular calmodulin and its association with epidermal growth factor in normal human body fluids. Journal of Endocrinology,118 501–509.

Neri, D., de Lalla, C., Petrul, H., Neri, P., & Winter, G. (1995). Calmodulin as a versatile tag for antibody fragments. BioTechnology, 13, pp. 373–377

Racioppi, L., Noeldner, P. K., Lin, F., Arvai, S., & Means, A. R. (2012). Calcium/calmodulin-dependent protein kinase kinase 2 regulates macrophage-mediated inflammatory responses. The Journal of Biological Chemistry,287(14), 11579-11591. doi:10.1074/jbc.M111.336032 [doi]

Ui-Tei, K., Nagano, M., Sato, S., & Miyata, Y. (2000). Calmodulin-dependent and -independent apoptosis in cell of a drosophila neuronal cell line. Apoptosis : An International Journal on Programmed Cell Death, 5(2), 133-140.

Wriggers, W., Mehler, E., Pitici, F., Weinstein, H., & Schulten, K. (1998). Structure and dynamics of Calmodulin in solution. Biophysical Journal, 74, 1622-1639.

Wolfe, D. M. D. M. (2006). Channeling studies in yeast: Yeast as a model for channelopathies? Neuromolecular Medicine, 8(3), 279; 279-306; 306.

Bagchi, Indrani, Qihu Huang, and Anthony Means. "Identification of Amino Acids Essential for Calmodulin Binding and Activation of Smooth Muscle Myosin Light Chain Kinas." THE JOURNAL OF BIOLOGICAL CHEMISTRY 267.February 15 (1992): 3024. Print.

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Sandbox 4465

From Proteopedia

Revision as of 04:21, 17 November 2015

Calmodulin

Calmodulin in the body

Structural Highlights

Function

References

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 </StructureSection>
 == References ==
-. Berridge, M. J., Lipp, P., & Bootman, M. D. (2000). The versatility and universality of calcium signalling. Nature Reviews Molecular Cell Biology, 1(1), 11-21. doi:10.1038/35036035
+Berridge, M. J., Lipp, P., & Bootman, M. D. (2000). The versatility and universality of calcium signalling. Nature Reviews Molecular Cell Biology, 1(1), 11-21. doi:10.1038/35036035
-. Eldik, L., & Watterson, D. (1998). Calmodulin and signal transduction. San Diego: Academic Press.
+Chan, K. F., & Chen, W. H. (1990). High performance capillary electrophoresis of calmodulin. Electrophoresis, 11(1), 15-18. doi:10.1002/elps.1150110104 [doi]
-. Huang, X., Liu, Y., Wang, R., Zhong, X., Liu, Y., Koop, A., Liu, Z. (2013). Two potential calmodulin-binding sequences in the ryanodine receptor contribute to a mobile, intra-subunit calmodulin-binding domain. Journal of Cell Science, 126(19), 4527–4535.
+Eldik, L., & Watterson, D. (1998). Calmodulin and signal transduction. San Diego: Academic Press.
-. Joseph, J. D., & Means, A. R. (2002). Calcium Binding Is Required for Calmodulin Function in Aspergillus nidulans. Eukaryotic Cell, 1(1), 119–125. http://doi.org/10.1128/EC.01.1.119-125.2002
+Huang, X., Liu, Y., Wang, R., Zhong, X., Liu, Y., Koop, A., Liu, Z. (2013). Two potential calmodulin-binding sequences in the ryanodine receptor contribute to a mobile, intra-subunit calmodulin-binding domain. Journal of Cell Science, 126(19), 4527–4535.
-. Lai, M., Brun, D., Edelstein, S. J., & Novere, N. L. (2015). Modulation of Calmodulin lobes by different targets: An allosteric model with hemi concerted conformational transitions. PLOS Computational Biology. http://doi:10.1371/journal.pcbi.1004063
+Joseph, J. D., & Means, A. R. (2002). Calcium Binding Is Required for Calmodulin Function in Aspergillus nidulans. Eukaryotic Cell, 1(1), 119–125. http://doi.org/10.1128/EC.01.1.119-125.2002
-. Lukas, T. J., Haiech, J., Lau, W., Craig, T. A., Zimmer, W. E., Shattuck, R. L., et al. (1988). Calmodulin and calmodulin-regulated protein kinases as transducers of intracellular calcium signals. Cold Spring Harbor Symposia on Quantitative Biology, 53 Pt 1, 185-193.
+Lai, M., Brun, D., Edelstein, S. J., & Novere, N. L. (2015). Modulation of Calmodulin lobes by different targets: An allosteric model with hemi concerted conformational transitions. PLOS Computational Biology. http://doi:10.1371/journal.pcbi.1004063
-. Neri, D., de Lalla, C., Petrul, H., Neri, P., & Winter, G. (1995). Calmodulin as a versatile tag for antibody fragments. BioTechnology, 13, pp. 373–377
+Lukas, T. J., Haiech, J., Lau, W., Craig, T. A., Zimmer, W. E., Shattuck, R. L., et al. (1988). Calmodulin and calmodulin-regulated protein kinases as transducers of intracellular calcium signals. Cold Spring Harbor Symposia on Quantitative Biology, 53 Pt 1, 185-193.
-. Wriggers, W., Mehler, E., Pitici, F., Weinstein, H., & Schulten, K. (1998). Structure and dynamics of Calmodulin in solution. Biophysical Journal, 74, 1622-1639.
+MacNeil S., Dawson RA., Crocker G., Barton CH., Hanford L., McGurk MR., and Munro DS.,(1988). Extracellular calmodulin and its association with epidermal growth factor in normal human body fluids. Journal of Endocrinology,118 501–509.
-. Wolfe, D. M. D. M. (2006). Channeling studies in yeast: Yeast as a model for channelopathies? Neuromolecular Medicine, 8(3), 279; 279-306; 306.
+Neri, D., de Lalla, C., Petrul, H., Neri, P., & Winter, G. (1995). Calmodulin as a versatile tag for antibody fragments. BioTechnology, 13, pp. 373–377
+Racioppi, L., Noeldner, P. K., Lin, F., Arvai, S., & Means, A. R. (2012). Calcium/calmodulin-dependent protein kinase kinase 2 regulates macrophage-mediated inflammatory responses. The Journal of Biological Chemistry,287(14), 11579-11591. doi:10.1074/jbc.M111.336032 [doi]
+Ui-Tei, K., Nagano, M., Sato, S., & Miyata, Y. (2000). Calmodulin-dependent and -independent apoptosis in cell of a drosophila neuronal cell line. Apoptosis : An International Journal on Programmed Cell Death, 5(2), 133-140.
+Wriggers, W., Mehler, E., Pitici, F., Weinstein, H., & Schulten, K. (1998). Structure and dynamics of Calmodulin in solution. Biophysical Journal, 74, 1622-1639.
+Wolfe, D. M. D. M. (2006). Channeling studies in yeast: Yeast as a model for channelopathies? Neuromolecular Medicine, 8(3), 279; 279-306; 306.
+Bagchi, Indrani, Qihu Huang, and Anthony Means. "Identification of Amino Acids Essential for Calmodulin Binding and Activation of Smooth Muscle Myosin Light Chain Kinas." THE JOURNAL OF BIOLOGICAL CHEMISTRY 267.February 15 (1992): 3024. Print.
 <references/>