Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Mar;86(5):1443–1447. doi: 10.1073/pnas.86.5.1443

Human muscle glycogen synthase cDNA sequence: a negatively charged protein with an asymmetric charge distribution.

M F Browner 1, K Nakano 1, A G Bang 1, R J Fletterick 1
PMCID: PMC286712  PMID: 2493642

Abstract

The cDNA for human muscle glycogen synthase encodes a protein of 737 amino acids. The primary structure of glycogen synthase is not related either to bacterial glycogen synthase or to any glycogen phosphorylase. All nine of the serines that are phosphorylated in the rabbit muscle enzyme in vivo are conserved in the human muscle sequence. The amino- and carboxyl-terminal fragments, which contain all the phosphorylation sites, are very negatively charged. Overall the unphosphorylated protein has a charge of -13, while the fully phosphorylated inactive protein has a net charge of -31. The importance of the asymmetrical charge distribution is discussed.

Full text

PDF
1443

Images in this article

1444Image
on p.1444
1446Image
on p.1446

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Camici M., DePaoli-Roach A. A., Roach P. J. Rabbit liver glycogen synthase. Purification and comparison of the properties of glucose-6-P-dependent and glucose-6-P-independent forms of the enzyme. J Biol Chem. 1984 Mar 25;259(6):3429–3434. [PubMed] [Google Scholar]
  2. Cohen P., Holmes C. F., Poulter L., Gibson B., Williams D. H. Identification of the C-terminus of rabbit skeletal muscle glycogen synthase. Biochem Biophys Res Commun. 1986 May 29;137(1):542–545. doi: 10.1016/0006-291x(86)91244-1. [DOI] [PubMed] [Google Scholar]
  3. Cohen P. Protein phosphorylation and hormone action. Proc R Soc Lond B Biol Sci. 1988 Jul 22;234(1275):115–144. doi: 10.1098/rspb.1988.0040. [DOI] [PubMed] [Google Scholar]
  4. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FRIEDMAN D. L., LARNER J. STUDIES ON UDPG-ALPHA-GLUCAN TRANSGLUCOSYLASE. III. INTERCONVERSION OF TWO FORMS OF MUSCLE UDPG-ALPHA-GLUCAN TRANSGLUCOSYLASE BY A PHOSPHORYLATION-DEPHOSPHORYLATION REACTION SEQUENCE. Biochemistry. 1963 Jul-Aug;2:669–675. doi: 10.1021/bi00904a009. [DOI] [PubMed] [Google Scholar]
  6. Finer-Moore J., Stroud R. M. Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor. Proc Natl Acad Sci U S A. 1984 Jan;81(1):155–159. doi: 10.1073/pnas.81.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fiol C. J., Mahrenholz A. M., Wang Y., Roeske R. W., Roach P. J. Formation of protein kinase recognition sites by covalent modification of the substrate. Molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. J Biol Chem. 1987 Oct 15;262(29):14042–14048. [PubMed] [Google Scholar]
  8. Gold A. M. Kinetic mechanism of rabbit muscle glycogen synthase I. Biochemistry. 1980 Aug 5;19(16):3766–3772. doi: 10.1021/bi00557a018. [DOI] [PubMed] [Google Scholar]
  9. Goldsmith E., Sprang S., Fletterick R. Structure of maltoheptaose by difference Fourier methods and a model for glycogen. J Mol Biol. 1982 Apr 5;156(2):411–427. doi: 10.1016/0022-2836(82)90336-9. [DOI] [PubMed] [Google Scholar]
  10. Hers H. G. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167–189. doi: 10.1146/annurev.bi.45.070176.001123. [DOI] [PubMed] [Google Scholar]
  11. Kaslow H. R., Lesikar D. D., Antwi D., Tan A. W. L-type glycogen synthase. Tissue distribution and electrophoretic mobility. J Biol Chem. 1985 Aug 25;260(18):9953–9956. [PubMed] [Google Scholar]
  12. Koenig M., Hoffman E. P., Bertelson C. J., Monaco A. P., Feener C., Kunkel L. M. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987 Jul 31;50(3):509–517. doi: 10.1016/0092-8674(87)90504-6. [DOI] [PubMed] [Google Scholar]
  13. Kumar A., Larsen C. E., Preiss J. Biosynthesis of bacterial glycogen. Primary structure of Escherichia coli ADP-glucose:alpha-1,4-glucan, 4-glucosyltransferase as deduced from the nucleotide sequence of the glgA gene. J Biol Chem. 1986 Dec 5;261(34):16256–16259. [PubMed] [Google Scholar]
  14. Lau K. H., Chen I. I., Thomas J. A. Dephosphorylation of glycogen synthase in rat heart extracts by E. coli alkaline phosphatase. Use of an exogenous phosphatase to study substrate-mediated regulation of dephosphorylation. Mol Cell Biochem. 1982 May 14;44(3):149–159. doi: 10.1007/BF00238503. [DOI] [PubMed] [Google Scholar]
  15. Leung P. S., Preiss J. Biosynthesis of bacterial glycogen: primary structure of Salmonella typhimurium ADPglucose synthetase as deduced from the nucleotide sequence of the glgC gene. J Bacteriol. 1987 Sep;169(9):4355–4360. doi: 10.1128/jb.169.9.4355-4360.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mahrenholz A. M., Wang Y. H., Roach P. J. Catalytic site of rabbit glycogen synthase isozymes. Identification of an active site lysine close to the amino terminus of the subunit. J Biol Chem. 1988 Aug 5;263(22):10561–10567. [PubMed] [Google Scholar]
  17. Nakano K., Hwang P. K., Fletterick R. J. Complete cDNA sequence for rabbit muscle glycogen phosphorylase. FEBS Lett. 1986 Aug 18;204(2):283–287. doi: 10.1016/0014-5793(86)80829-8. [DOI] [PubMed] [Google Scholar]
  18. Newgard C. B., Littman D. R., van Genderen C., Smith M., Fletterick R. J. Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes. J Biol Chem. 1988 Mar 15;263(8):3850–3857. [PubMed] [Google Scholar]
  19. Newgard C. B., Nakano K., Hwang P. K., Fletterick R. J. Sequence analysis of the cDNA encoding human liver glycogen phosphorylase reveals tissue-specific codon usage. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8132–8136. doi: 10.1073/pnas.83.21.8132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Palm D., Goerl R., Burger K. J. Evolution of catalytic and regulatory sites in phosphorylases. Nature. 1985 Feb 7;313(6002):500–502. doi: 10.1038/313500a0. [DOI] [PubMed] [Google Scholar]
  21. Picton C., Aitken A., Bilham T., Cohen P. Multisite phosphorylation of glycogen synthase from rabbit skeletal muscle. Organisation of the seven sites in the polypeptide chain. Eur J Biochem. 1982 May;124(1):37–45. doi: 10.1111/j.1432-1033.1982.tb05903.x. [DOI] [PubMed] [Google Scholar]
  22. Pitcher J., Smythe C., Campbell D. G., Cohen P. Identification of the 38-kDa subunit of rabbit skeletal muscle glycogen synthase as glycogenin. Eur J Biochem. 1987 Dec 15;169(3):497–502. doi: 10.1111/j.1432-1033.1987.tb13637.x. [DOI] [PubMed] [Google Scholar]
  23. Poulter L., Ang S. G., Gibson B. W., Williams D. H., Holmes C. F., Caudwell F. B., Pitcher J., Cohen P. Analysis of the in vivo phosphorylation state of rabbit skeletal muscle glycogen synthase by fast-atom-bombardment mass spectrometry. Eur J Biochem. 1988 Aug 15;175(3):497–510. doi: 10.1111/j.1432-1033.1988.tb14222.x. [DOI] [PubMed] [Google Scholar]
  24. Preiss J. Bacterial glycogen synthesis and its regulation. Annu Rev Microbiol. 1984;38:419–458. doi: 10.1146/annurev.mi.38.100184.002223. [DOI] [PubMed] [Google Scholar]
  25. Rodriguez I. R., Whelan W. J. A novel glycosyl-amino acid linkage: rabbit-muscle glycogen is covalently linked to a protein via tyrosine. Biochem Biophys Res Commun. 1985 Oct 30;132(2):829–836. doi: 10.1016/0006-291x(85)91206-9. [DOI] [PubMed] [Google Scholar]
  26. Rulfs J., Wolleben C. D., Miller T. B., Johnson G. L. Immunologic identification of a glycogen synthase 93,000-dalton subunit from rat heart and liver. J Biol Chem. 1985 Jan 25;260(2):1203–1207. [PubMed] [Google Scholar]
  27. Sprang S. R., Acharya K. R., Goldsmith E. J., Stuart D. I., Varvill K., Fletterick R. J., Madsen N. B., Johnson L. N. Structural changes in glycogen phosphorylase induced by phosphorylation. Nature. 1988 Nov 17;336(6196):215–221. doi: 10.1038/336215a0. [DOI] [PubMed] [Google Scholar]
  28. Svensson B. Regional distant sequence homology between amylases, alpha-glucosidases and transglucanosylases. FEBS Lett. 1988 Mar 28;230(1-2):72–76. doi: 10.1016/0014-5793(88)80644-6. [DOI] [PubMed] [Google Scholar]
  29. Tagaya M., Nakano K., Fukui T. A new affinity labeling reagent for the active site of glycogen synthase. Uridine diphosphopyridoxal. J Biol Chem. 1985 Jun 10;260(11):6670–6676. [PubMed] [Google Scholar]
  30. Wang Y. H., Bell A. W., Hermodson M. A., Roach P. J. Liver isozyme of rabbit glycogen synthase. Amino acid sequences surrounding phosphorylation sites recognized by cyclic AMP-dependent protein kinase. J Biol Chem. 1986 Dec 25;261(36):16909–16915. [PubMed] [Google Scholar]
  31. Yu F., Jen Y., Takeuchi E., Inouye M., Nakayama H., Tagaya M., Fukui T. Alpha-glucan phosphorylase from Escherichia coli. Cloning of the gene, and purification and characterization of the protein. J Biol Chem. 1988 Sep 25;263(27):13706–13711. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES