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The Biologic Action of Single-chain Choriogonadotropin Is Not Dependent on the Individual Disulfide Bonds of the β Subunit
Disrupting disulfide loops in the human chorionic gonadotropin β subunit (CGβ) inhibits combination with the α subunit. Because the bioactivity requires a heterodimer, studies on the role of disulfide bonds on receptor binding/signal transduction have previously been precluded. To address this pr...
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| Published in: | The Journal of biological chemistry 1997-03, Vol.272 (11), p.6827 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
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| Summary: | Disrupting disulfide loops in the human chorionic gonadotropin β subunit (CGβ) inhibits combination with the α subunit. Because
the bioactivity requires a heterodimer, studies on the role of disulfide bonds on receptor binding/signal transduction have
previously been precluded. To address this problem, we bypassed the assembly step and genetically fused CGβ subunits bearing
paired cysteine mutations to a wild-type α (WTα) subunit. The changes altered secretion of the single-chain mutants which
parallel that seen for the CGβ monomeric subunit. Despite conformational changes in CG disulfide bond mutants (assayed by
gel electrophoresis and conformationally sensitive monoclonal antibodies), the variants bind to the lutropin/CG receptor and
activated adenylate cyclase in vitro The data show that the structural requirements for secretion and bioactivity are not the same. The results also suggest that
the extensive native subunit interactions determined by the cystine bonds are not required for signal transduction. Moreover,
these studies demonstrate that the single-chain model is an effective approach to structure-activity relationships of residues
and structural domains associated with assembly of multisubunit ligands. |
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| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.272.11.6827 |