Role of disulphide bond formation in folding, secretion, and assembly of human chorionic gonadotropin subunits

Elliott Bedows, Ryan J. Darling, Jason A. Wilken, Simon Sherman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Ability of a glycoprotein hormone to fold and assemble correctly is an essential requirement for the attainment of its biological activity. Cells have a quality control system to assure that when proteins of the endoplasmic reticulum misfold or fail to assemble correctly they do not exit the cell. But human chorionic gonadotropin (hCG) is an exception to this rule as is illustrated by the following observations. First, both hCG subunits are secreted efficiently as unassembled monomers. Second, some mis(un)folded forms of hCG-β can be efficiently secreted from cells that do not facilitate the secretion of other misfolded proteins. Third, the efficient secretion of an assembly incompetent α-subunit occurs in spite of lacking both of its non-cystine knot disulphide bonds. And fourth, hCG heterodimers that contain misfolded α-subunits as a result of lacking cystine knot disulphides are also secreted. In this report, we review direct experimental evidence demonstrating that the structural requirements necessary for the secretion of hCG subunits differ from the structural requirements necessary for hCG assembly by using disulphide bond formation as an index with which to monitor the folding, assembly, and secretion of hCG and its α- and β-subunits.

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalIndian journal of experimental biology
Volume40
Issue number4
StatePublished - Jan 1 2002

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Chorionic Gonadotropin
Disulfides
Cystines
Proteins
Glycoproteins
Cystine
Hormones
Bioactivity
Gonadotropins
Endoplasmic Reticulum
Quality Control
Quality control
Monomers
Control systems

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Cell Biology

Cite this

Role of disulphide bond formation in folding, secretion, and assembly of human chorionic gonadotropin subunits. / Bedows, Elliott; Darling, Ryan J.; Wilken, Jason A.; Sherman, Simon.

In: Indian journal of experimental biology, Vol. 40, No. 4, 01.01.2002, p. 467-476.

Research output: Contribution to journalArticle

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