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Bifunctional hCG analogs adopt different conformations in LH and FSH receptor complexes.
Wang, Y; Bernard, M P; Moyle, W R.
Afiliação
  • Wang Y; Department of Obstetrics and Gynecology, Robert Wood Johnson (Rutgers) Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Mol Cell Endocrinol ; 170(1-2): 67-77, 2000 Dec 22.
Article em En | MEDLINE | ID: mdl-11162891
Human reproduction requires specific interactions between follitropin (hFSH) and its receptor (FSHR) and between lutropin (hLH) or choriogonadotropin (hCG) and the lutropin receptor (LHR). Substitution of hFSH residues between hCG beta-subunit cysteines 11-12 creates a bifunctional analog that binds both receptors. To understand the basis of this observation, we used antibody probes to compare the conformations of bifunctional analogs before and after they were complexed with each receptor. Introduction of hFSH residues between cysteines 11-12 changed a distant conformation-sensitive region created by the juxtaposition of the subunit aminotermini. This region, found not to contact either receptor, was altered further when bifunctional ligands bound FSHR. All other surfaces, detected in LHR complexes, were also recognized in FSHR complexes, an indication that bifunctional ligands bind both receptors in similar orientations. These observations suggest that unlike hCG or hFSH, bifunctional gonadotropins can acquire "lutropin" and "follitropin" conformations, a phenomenon accentuated by receptor contacts.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores do FSH / Receptores do LH / Gonadotropina Coriônica Limite: Humans Idioma: En Ano de publicação: 2000 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores do FSH / Receptores do LH / Gonadotropina Coriônica Limite: Humans Idioma: En Ano de publicação: 2000 Tipo de documento: Article