Disulfide bonding controls the processing of retro viral envelope glycoproteins

Brian C. Gliniak, Susan L. Kozak, Richard T. Jones, David Kabat

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The mitogenic membrane glycoprotein (gp55) encoded by Friend erythroleukemia virus is inefficiently processed from the rough endoplasmic reticulum (RER) and only 3-5% reaches plasma membranes. Because this processed component (gp55P) contains larger and more complex oligosaccharides, it can be separated from RER gp55. In nonreducing conditions, gp55P is a unique disulfide-bonded dimer, whereas RER gp55 consists of monomers and dimers with diverse intrachain and interchain disulfide bonds. This suggests that gp55 folds heterogeneously and that only one homodimer is competent for export from the RER. Pulse-chase analyses of gp55 components labeled with radioactive amino acids indicated that formation of diverse disulfide-bonded components occurred within minutes of polypeptide synthesis and that malfolded components did not later isomerize to generate dimers competent for export from the RER. Chemical studies suggested that all 12 cysteines of gp55 were oxidized within 5 min after synthesis of the protein. In contrast, the envelope glycoprotein precursor (gPr90) encoded by a replication-competent murine leukemia virus folds more homogeneously, and it is then processed and cleaved to form an extracellular glycoprotein gp70 plus a transmembrane protein p15E. The fully processed glycoprotein contains an unoxidized cysteine sulfhydryl that isomerizes reversibly with a disulfide bond that links gp70 to p15E. Consequently, only a proportion of gp70 and p15E is disulfide-bonded, and dissociation occurs when the environment becomes even slightly reducing. The gp55 glycoprotein appears to be an extreme example of protein malfolding associated with imprecise and irreversible disulfide bonding. We discuss evidence that folding inefficiencies are common for retroviral proteins that have newly evolving pathogenic functions.

Original languageEnglish (US)
Pages (from-to)22991-22997
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number34
StatePublished - Dec 5 1991

Fingerprint

Rough Endoplasmic Reticulum
Disulfides
Glycoproteins
Processing
Dimers
Viruses
Cysteine
Proteins
Friend murine leukemia virus
Murine Leukemia Viruses
Leukemia, Erythroblastic, Acute
Membrane Glycoproteins
Cell membranes
Oligosaccharides
Monomers
Cell Membrane
Amino Acids
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Gliniak, B. C., Kozak, S. L., Jones, R. T., & Kabat, D. (1991). Disulfide bonding controls the processing of retro viral envelope glycoproteins. Journal of Biological Chemistry, 266(34), 22991-22997.

Disulfide bonding controls the processing of retro viral envelope glycoproteins. / Gliniak, Brian C.; Kozak, Susan L.; Jones, Richard T.; Kabat, David.

In: Journal of Biological Chemistry, Vol. 266, No. 34, 05.12.1991, p. 22991-22997.

Research output: Contribution to journalArticle

Gliniak, BC, Kozak, SL, Jones, RT & Kabat, D 1991, 'Disulfide bonding controls the processing of retro viral envelope glycoproteins', Journal of Biological Chemistry, vol. 266, no. 34, pp. 22991-22997.
Gliniak BC, Kozak SL, Jones RT, Kabat D. Disulfide bonding controls the processing of retro viral envelope glycoproteins. Journal of Biological Chemistry. 1991 Dec 5;266(34):22991-22997.
Gliniak, Brian C. ; Kozak, Susan L. ; Jones, Richard T. ; Kabat, David. / Disulfide bonding controls the processing of retro viral envelope glycoproteins. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 34. pp. 22991-22997.
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