Complex glycoproteins

Worton, R., 1995. Mnscnlar dystrophies Diseases of die dystrophin-glycoprotein complex. Science 270 755-756. 

This fraction was termed Haemonchus galactose-containing glycoprotein complex (H-gal-GP). The microvillar surface of the intestinal cells of worms retrieved from vaccinated lambs was coated with sheep immunoglobulin and protection observed, over a series of trials, was correlated with systemic antibody titre (Smith et al., 1999). 

Rocha, J. and Munn, E.A. (1997) P150, a protective glycoprotein complex of the microvillar membrane of Haemonchus contortus. Conference Abstract from Parasitic Helminths - from Genomes to Vaccines, Edinburgh, UK, 6-9 September 1997. 

Smith, S.K. and Smith, W.D. (1996) Immunisation of sheep with an integral membrane glycoprotein complex of Haemonchus contortus and its major polypeptide components. Research in Veterinary Science 60, 1-6. 

Functionally, dystrophin is associated with a glycoprotein complex embedded within the sarcolemma, where it acts to help maintain the shape and integrity of each myocyte and is also involved with cell signalling. Boys with DMD typically have less than 5% of the normal amount of functionally active dystrophin whereas in the less severe BMD there may be more than 20% of the protein present. All muscles are affected so not only movement but also breathing becomes impaired. 

Bleomycin is a naturally occurring fermentation product of Streptomyces verticillus. It is a basic glycoprotein, complexed with Cu++. It intercalates between DNA base pairs, and it also chelates iron, generating oxygen radicals which further damage the DNA. It is the only cell-cycle specific agent among the antibiotics as it causes accumulation of cells in the G2 phase of the cell cycle. 

Factor VIII. Originally known as antihemophilic globulin, Factor VIII is a very large glycoprotein complex of two different molecular units... 

While one end of the dystrophin molecule binds to actin filaments, the C-terminal domain associates with several additional proteins to form a dystrophin-glycoprotein complex (see figure)/1 k Dystrophin is linked directly to the membrane-spanning protein P-dystroglycan, which in the outer membrane surfaces associates with a glycoprotein a-dystroglycan. The latter binds to laminin-2 (Fig. 8-33), a protein that binds the cell to the basal lamina. Four... 

Schematic model of the dystrophin-glycoprotein complex. Courtesy of Kevin P. Campbell. See Lim and Campbell1 Abbreviations LGMD, Limb Girdle muscular dystrophy CMD, congenital muscular dystrophy DMD / BMD, Duchenne / Becker muscular dystrophies.

A small number of cases have been identified in which there is a deletion of the carboxy-terminus of dystrophin. In these patients, it is common for the mutant protein to localize to the sarcolemma (Bies et al., 1992 Helliwell et al., 1992 Hoffman et al., 1991). These cases are good examples of the importance of the cysteine-rich and C-terminal domains of dystrophin, presumably reflecting the importance of interactions with components of the dystrophin-associated glycoprotein complex. Many single point mutations within dystrophin are also known. 

Ervasti, J. M., and Campbell, K. P. (1993b). A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. J. Cell Biol. 122, 809-823. 

Ran do, T. A. (2001). The dystrophin-glycoprotein complex, cellular signaling, and the regulation of cell survival in the muscular dystrophies. Muscle Nerve 24, 1575-1594. 

Keywords dystrophin-glycoprotein complex, sarcolemma, membrane tears, calcium channels,... 

Figure 1. The muscle dystrophin-glycoprotein complex. The dystrophin-glycoprotein complex normally spans the plasma membrane of the skeletal muscle cell and may stabilize the sarcolemma and cytoskeleton to allow force transduction between the intracellular cytoskeleton (F-actin filaments) and the extracellular matrix. The molecules indicated are core components of the dystrophin-glycoprotein complex. Laminin 2 is the predominant laminin isoform in skeletal muscle basement membranes. Modified from McNeil and Steinhardt (2003)...

Cox, G.A., Sunada, Y., Campbell, K.P., and Chamberlain, J.S., 1994, Dp71 can restore the dystrophin-associated glycoprotein complex in muscle but fails to prevent dystrophy, Nat Genet, 8, pp 333-339. 

Halayko, A.J., and Stelmack, G.L., 2005, The association of caveolae, actin, and the dystrophin-glycoprotein complex a role in smooth muscle phenotype and function , Can J Physiol Pharmacol, 83, pp 877-891. 

Rybakova, I.N., and Ervasti, J.M., 1997, Dystrophin-glycoprotein complex is monomeric and stabilizes actin filaments in vitro through a lateral association, J Biol Chem, 272, pp 28771-28778. 

Suzuki, A., Yoshida, M., Hayashi, K., Mizuno, Y., Hagiwara, Y., and Ozawa, E., 1994, Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin, Eur J Biochem, 220, pp 283—292. 

Galbiati, F., Engelman, J. A., Volonte, D., Zhang, X. L., Minetti, C., Li, M., et al. (2001) Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and t-tubule abnormalities. J Biol Chem 276,21425-21433. 

Yue, Y. P., Li, Z. B., Harper, S. Q. et al. (2003). Microdystrophin gene therapy of cardiomyopathy restores dystrophin-glycoprotein complex and improves sarcolemma integrity in the mdx mouse heart. Circulation 108(13), 1626-1632. 

Li, Y., Hua, F., Carraway, K.L., and Carothers Carraway, C.A. 1999. The pl85" -contain-ing glycoprotein complex of a microfilament-associated signal transduction particle. Purification, reconstitution, and molecular associations with p58 and actin. J Biol Chem 274(36) 25651-25658. 

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