Abstract
Ubiquitin is a small (76 amino acid) protein found in all eukaryotes either free or covalently attached to proteins in the nucleus, cytosol, or plasma membrane (Wilkinson, 1986; Busch, 1984; Hershko, 1988). It is the most highly conserved protein yet discovered in eukaryotes, with only three conservative amino acid substitutions separating yeast ubiquitin from the human (Fig. 1). The protein is water soluble, extremely stable, and may be boiled without loss of activity. Ubiquitin is stable to proteases and has not been shown to be glycosylated (Ozkaynak et al., 1984; Vierstra et al., 1986; Schlesinger and Goldstein, 1975). It contains no cysteine and only one histidine at position 68. The crystal structure of human ubiquitin has been solved at 1.8 Å resolution and demonstrates that ubiquitin is a compact molecule with a hydrophobic core containing three and one-half turns of α helix and five strands of β sheet. At the carboxy terminus, four amino acids protrude from the core of the molecule and have considerable freedom of motion (Vijay-Kumar et al., 1987).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bachmair, A., Finley, D., and Varshaysky, A., 1986, In vivo half-life of a protein is a function of its amino-terminal residue, Science 234: 179–186.
Baker, R. T., and Board, P. G., 1987, The human ubiquitin gene family: Structure of a gene and pseudogenes from the UbB subfamily, Nucleic Acid Res. 15: 443–463.
Ball, E., Karlik, C. C., Beall, C. J., Saville, D. L., Sparrow, J. C., Bullard, B., and Fryberg, E. A., 1987, Arthrin, a myofibrillar protein of insect flight muscle, is an actin-ubiquitin conjugate, Cell 51: 221–228.
Bond, U., and Schlesinger, M. J., 1985, Ubiquitin is a heat shock protein in chicken embryo fibroblasts, Mol. Cell. Biol. 5: 949–956.
Busch, H., 1984, Ubiquitination of proteins, Methods Enzymol. 106: 238–262.
Butt, T. R., Khan, M. I., Marsh, J., Ecker, D. J., and Crooke, S. T., 1988, Ubiquitin-metallothionein fusion protein expression in yeast, J. Biol. Chem. 263: 16364–16371.
Butt, T. R., Jonnalagadda, S., Monia, B. P., Sternberg, E. J., Marsh, J. A., Stadel, J., Ecker, D. J., and Crooke, S. T., 1989, Ubiquitin fusion augments the yield of cloned gene products in Escherichia coli. Proc. Natl. Acad. Sci. USA 86: 2540–2544.
Ciechanover, A., 1987, Regulation of the ubiquitin-mediated proteolytic pathway: Role of the substrate a-NH2 group and of transfer RNA, J. Cell. Biochem. 34: 81–100.
Ciechanover, A., Finley, D., and Varshaysky, A., 1984, Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85, Cell 37: 57–66.
Dworkin-Rastl, E., Shrutkowski, A., and Dworkin, M. B., 1984, Multiple ubiquitin mRNAs during Xenopus laevis development contain tandem repeats of the 76 amino acid coding sequence, Cell 39: 321–325.
Ecker, D. J., Khan, M. I., Marsh, J., Butt, T. R., and Crooke, S. T., 1987a, Chemical synthesis and expression of a cassette adapted ubiquitin gene, J. Biol. Chem. 262: 3524–3527.
Ecker, D. J., Butt, T. R., Marsh, J., Sternberg, E. J., Margolis, N., Monia, B. P., Jonnalagadda, S., Khan, M. I., Weber, P. L., Mueller, L., and Crooke, S. T., 1987b, Gene synthesis, expression, structures, and functional activities of site-specific mutants of ubiquitin, J. Biol. Chem. 262: 14213–14221.
Ecker, D. J., Butt, T. R., Marsh, J., Sternberg, E. J., Dixon, J. S., Weber, P. L., and Crooke, S. T., 1989, Ubiquitin function studied by disulfide engineering, J. Biol. Chem. 264: 1887–1893.
Finley, D., Ciechanover, A., and Varshaysky, A., 1984, Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85, Cell 37: 43–55.
Finley, D., Ozkaynak, O., and Varshaysky, A., 1987, The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses, Cell 48: 1035–1046.
Gausing, K., and Barkardottir, R., 1986, Structure and expression of ubiquitin genes in higher plants, Eur. J. Biochem. 158: 57–62.
Hershko, A., 1988, Ubiquitin-mediated protein degradation, J. Biol. Chem. 263: 15237–15240.
Hershko, A., and Ciechanover, A., 1986, Transfer RNA is an essential component of the ubiquitin and ATP-proteolytic system, Prog. Nucleic Acid Res. Mol. Biol. 33: 19–56.
Izquierdo, M., Ambas, C., Galceran, J. Burke, J., and Cabrera, V. M., 1984, Characterization of a Drosophila repeat mapping at the early-ecdysone puff 63F and present in many eukaryotic genomes, Biochim. Biophys. Acta 783: 114–121.
Jonnalagadda, S., Ecker, D. J., Sternberg, E. J., Butt, T. R., and Crooke, S. T., 1988, Ubiquitin carboxyl-terminal peptides, J. Biol. Chem. 263: 5016–5019.
Jonnalagadda, S., Butt, T. R., Monia, B. P., Mirabelli, C. K., Gotlib, L., Ecker, D. J., and Crooke, S. T., 1989, Multiple (a-NH-ubiquitin) protein endoproteases in cells, J. Biol. Chem. 264: 10637–10642.
Lund, P. K., Moats-Staats, B. M., Simmons, J. G., Hoyt, E., D’Ercole, A. J., Martin, F., and Van Wyk, J. J., 1985, Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor, J. Biol. Chem. 260: 7609–7613.
Miller, J., McLachlan, A. D., and Klug, A., 1985, Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes, EMBO J. 4: 1609–1614.
Monia, B. P., Ecker, D J, Jonnalagadda, S., Marsh, J., Gotlib, L., Butt, T. R., and Crooke, S. T., 1989, Gene synthesis, expression, and processing of human ubiquitin carboxyl extension proteins, J. Biol. Chem. 264: 4093–4103.
Mori, H., Kondo, J., and Ihara, Y., 1987, Ubiquitin is a component of paired helical filaments in Alzheimer’s disease, Science 235: 1641–1644.
Okabe, T., Fujisawa, M., Mihara, A., Sato, S., Fujiyoshi, N., and Takaku, F., 1986, Amino-terminal amino acid sequence of a novel autocrine growth factor: Homology with ubiquitin, J. Cell Biol. 103: 442a.
Ozkaynak, E., Finley, D., and Varshaysky, A., 1984, The yeast ubiquitin gene: head-to-tail repeats encoding a polyubiquitin precursor protein, Nature 213: 663–666.
Ozkaynak, E., Finley, D., Solomon, M., and Varshaysky, A., 1987, The yeast ubiquitin genes: A family of natural gene fusions, EMBO J. 6: 1429–1439.
Rechsteiner, M., 1987, Ubiquitin-mediated pathways for intracellular proteolysis, Annu. Rev. Cell Biol. 3: 1–30.
Rechsteiner, M. (ed.), 1988, Ubiquitin, Plenum Press, New York.
Rhodes, D., and Klug, A., 1986, An underlying repeat in some transcriptional control sequences corresponding to half a double helical turn of DNA, Cell 46: 123–132.
Schlesinger, D. H., and Goldstein, G., 1975, Molecular conservation of 74 amino acid sequence of ubiquitin between cattle and man, Nature 255: 423–424.
Vierstra, R. D., Langan, S. M., and Schaller, G. E., 1986, Complete amino acid sequence of ubiquitin from the higher plant Avena sativa, Biochemistry 25: 3105–3108.
Vijay-Kumar, S., Bugg, C. E., and Cook, W. J., 1987, Structure of ubiquitin refined at 1.8 resolution, J. Mol. Biol. 194: 531–544.
Wilborg, O., Pedersen, M. S., Wind, A., Berglund, L. E., Marcker, K. A., and Vuust, J., 1985, The human ubiquitin multigene family: some genes contain multiple directly repeated ubiquitin coding sequences, EMBO J. 4: 755–759.
Wilkinson, K. D., and Mayer, A. N., 1986, Alcohol-induced conformational changes of ubiquitin, Arch. Biochem. Biophys. 250: 390–399.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Plenum Press, New York
About this chapter
Cite this chapter
Crooke, S.T. et al. (1990). Studies on the Structure and Function of Ubiquitin. In: Hook, J.B., Poste, G., Schatz, J. (eds) Protein Design and the Development of New Therapeutics and Vaccines. New Horizons in Therapeutics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5739-1_20
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5739-1_20
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5741-4
Online ISBN: 978-1-4684-5739-1
eBook Packages: Springer Book Archive