Home LiteratureArticle Details
PMID: 6584901 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Biogenesis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an integral glycoprotein of the endoplasmic reticulum.

Brown DA, Simoni RD

Abstract

Using a cell line, C100, that overproduces 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase; EC 1.1.1.34) 100-fold, we have studied the synthesis and insertion of this protein into the endoplasmic reticulum. The enzyme is synthesized on membrane-bound polysomes. It is cotranslationally but not post-translationally inserted into dog pancreatic microsomes. This cotranslational insertion is dependent upon signal recognition particle. HMG-CoA reductase is glycosylated with an oligosaccharide(s) of the "high-mannose" type sensitive to endo-beta-D-N-acetylglucosaminidase H. Partial determination of the NH2-terminal amino acid sequence of the in vitro translation product and the mature polypeptide indicate they are the same and demonstrate there is no cleavage of an NH2-terminal signal sequence.

MeSH Terms
Amino Acid Sequence Animals Cell Line Cricetinae Dogs Endoplasmic Reticulum/metabolism Glycoproteins/biosynthesis Hydroxymethylglutaryl CoA Reductases/biosynthesis Intracellular Membranes/metabolism Membrane Proteins/biosynthesis Peptides/metabolism Polyribosomes/metabolism Protein Biosynthesis Protein Precursors/metabolism Protein Sorting Signals
Chemicals
Glycoproteins Membrane Proteins Peptides Protein Precursors Protein Sorting Signals Hydroxymethylglutaryl CoA Reductases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Brown D A
Simoni R D
References (30)
30 references, click to expand
  1. Role of a hydrophobic polypeptide in the N-terminal region of NADPH-cytochrome P-450 reductase in complex formation with P-450LM.
    Biochem Biophys Res Commun. 1979 Dec 28;91(4):1528-35 PMID: 118758
  2. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  3. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose.
    Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408-12 PMID: 4504350
  4. Amplification of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, but not for the 53-kDa protein, in UT-1 cells.
    J Biol Chem. 1983 Jul 10;258(13):8462-9 PMID: 6863296
  5. Inhibition of the transition of a 40 S ribosome-Met-tRNA-i-Met complex to an 80 S ribosome-Met-tRNA-i-Met- complex by 7-Methylguanosine-5'-phosphate.
    Nature. 1976 Mar 25;260(5549):359-60 PMID: 1256580
  6. Early auxin-regulated polyadenylylated mRNA sequences in pea stem tissue.
    Proc Natl Acad Sci U S A. 1982 Jan;79(2):418-21 PMID: 16593146
  7. Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein.
    J Cell Biol. 1981 Nov;91(2 Pt 1):545-50 PMID: 7309795
  8. Proteinase involvement in the solubilization of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
    Biochem Biophys Res Commun. 1981 Sep 16;102(1):81-5 PMID: 7030342
  9. Mevalonolactone inhibits the rate of synthesis and enhances the rate of degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat hepatocytes.
    J Biol Chem. 1983 Jun 25;258(12):7272-5 PMID: 6863245
  10. Isolation and characterization of cells resistant to ML236B (compactin) with increased levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
    J Biol Chem. 1981 Jul 10;256(13):6762-8 PMID: 7240242
  11. Effect of tunicamycin on 3-hydroxy-3-methylglutaryl coenzyme A reductase in C-6 glial cells.
    J Biol Chem. 1983 Aug 10;258(15):9220-6 PMID: 6874686
  12. The use of intensifying screens or organic scintillators for visualizing radioactive molecules resolved by gel electrophoresis.
    Methods Enzymol. 1980;65(1):363-71 PMID: 7374459
  13. Intracellular protein topogenesis.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496-500 PMID: 6929499
  14. Appearance of crystalloid endoplasmic reticulum in compactin-resistant Chinese hamster cells with a 500-fold increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
    Proc Natl Acad Sci U S A. 1982 Feb;79(4):1185-9 PMID: 6951166
  15. An efficient mRNA-dependent translation system from reticulocyte lysates.
    Eur J Biochem. 1976 AUG 1;67(1):247-56 PMID: 823012
  16. Translocation of proteins across the endoplasmic reticulum III. Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes.
    J Cell Biol. 1981 Nov;91(2 Pt 1):557-61 PMID: 7309797
  17. Preparation of delipidized serum protein for use in cell culture systems.
    In Vitro. 1976 Aug;12(8):554-7 PMID: 992668
  18. Efficient cleavage and segregation of nascent presecretory proteins in a reticulocyte lysate supplemented with microsomal membranes.
    J Biol Chem. 1978 Jun 10;253(11):3753-6 PMID: 649601
  19. Secretory protein translocation across membranes-the role of the "docking protein'.
    Nature. 1982 Jun 24;297(5868):647-50 PMID: 7088152
  20. Overproduction of a Mr 92,000 protomer of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in compactin-resistant C100 cells.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1516-20 PMID: 6572913
  21. 3-Hydroxy-3-methylglutaryl-CoA reductase: a transmembrane glycoprotein of the endoplasmic reticulum with N-linked "high-mannose" oligosaccharides.
    Proc Natl Acad Sci U S A. 1983 Dec;80(23):7165-9 PMID: 6580634
  22. Messenger RNA for myosin polypeptides: isolation from single myogenic cell cultures.
    Cell. 1977 Feb;10(2):265-73 PMID: 837449
  23. 3-Hydroxy-3-methylglutaryl coenzyme A reductase. Solubilization and purification of a cold-sensitive microsomal enzyme.
    J Biol Chem. 1973 Jul 10;248(13):4731-8 PMID: 4146267
  24. Purification of a membrane-associated protein complex required for protein translocation across the endoplasmic reticulum.
    Proc Natl Acad Sci U S A. 1980 Dec;77(12):7112-6 PMID: 6938958
  25. Protein transfer across microsomal membranes reassembled from separated membrane components.
    Nature. 1978 Jun 15;273(5663):569-71 PMID: 96350
  26. Studies on the biosynthesis of microsomal membrane proteins. Site of synthesis and mode of insertion of cytochrome b5, cytochrome b5 reductase, cytochrome P-450 reductase and epoxide hydrolase.
    Eur J Biochem. 1982 Feb;122(2):393-402 PMID: 6800789
  27. N-Linked glycoprotein assembly. Evidence that oligosaccharide attachment occurs within the lumen of the endoplasmic reticulum.
    J Biol Chem. 1980 Apr 25;255(8):3600-4 PMID: 7364760
  28. Molecular cloning of 3-hydroxy-3-methylglutaryl coenzyme a reductase and evidence for regulation of its mRNA.
    Proc Natl Acad Sci U S A. 1982 Dec;79(24):7704-8 PMID: 6961444
  29. Synthesis and insertion of cytochrome P-450 into endoplasmic reticulum membranes.
    Proc Natl Acad Sci U S A. 1980 Feb;77(2):965-9 PMID: 6767247
  30. A procedure for the quantitative recovery of homogeneous populations of undegraded free and bound polysomes from rat liver.
    Biochemistry. 1976 Apr 20;15(8):1704-12 PMID: 1268192
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1984-03-00
Pages
1674-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC344980
Subset
IM
Grants
NIGMS NIH HHS · GM07276 · United States
NHLBI NIH HHS · HL26502 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com