title: Disulfide bonds 7-31 and 59-87 of the alpha-subunit play a different role in assembly of human chorionic gonadotropin and lutropin.
abstract: CG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit but differ in their hormone-specific beta-subunits. Both subunits have five and six disulfide bonds, respectively, which consists of cystine knot structure. We previously eliminated the disulfide bonds 7-31 and 59-87 in alpha-subunit without significantly affecting assembly with human CG beta-subunit. To study the role of these disulfide bonds in dimerization with other beta-subunits, the wild-type or mutated alpha gene was contransfected with the wild-type human LH beta or FSH beta gene into Chinese hamster ovary (CHO) cells or GH3 cells, and assembly was assessed by continuous labeling with [35S]methionine/cysteine, immunoprecipitation with anti-alpha or-beta serum, and SDS-PAGE. Our data revealed that disruption of either disulfide bond 7-31 or 59-87 in the alpha-subunit markedly reduced the dimer formation with LH beta-subunit in both CHO and GH3 cells, whereas it did not significantly affect the assembly of FSH. This suggests that the regions in the alpha-subunit recognized by beta-subunits for assembly are different among gonadotropins.
authors.affiliation: Department of Obstetrics and Gynecology, Handa City Hospital, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Furuhashi
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Suganuma
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000737:chemistry*; D006224:Cricetinae; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry*; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D007986:Luteinizing Hormone / Q000737:chemistry*; D017510:Protein Folding
chemical_list: D006063:Chorionic Gonadotropin; D004220:Disulfides; D015292:Glycoprotein Hormones, alpha Subunit; D007986:Luteinizing Hormone