title: A portable site: a binding element for 17β-estradiol can be placed on any subunit of a nicotinic α4β2 receptor.
abstract: Endogenous steroids can modulate the activity of transmitter-gated channels by directly interacting with the receptor. 17β-Estradiol potentiates activation of neuronal nicotinic α4β2 receptors by interacting with a 4 aa sequence at the extreme C terminus of the α4 subunit, but it is not known whether potentiation requires that the sequence be placed on a specific subunit (e.g., an α4 subunit that is involved in forming an acetylcholine-binding site). By using concatemers of subunits and chimeric subunits, we have found that the C-terminal domain can be moved from the α4 to the β2 subunit and still result in potentiation. In addition, the sequence can be placed on a subunit that contributes to an acetylcholine-binding site or on the structural subunit. The data indicate that this estradiol-binding element is a discrete sequence and suggest that the effect of 17β-estradiol is mediated by actions on single subunits and that the overall consequences for gating occur because of the summation of independent energetic contributions to overall gating of this receptor.
authors: Department of Anesthesiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
authors: Xiaochun
authors: X
authors: Jin
authors: Joe Henry
authors: JH
authors: Steinbach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
chemical_list: D021122:Protein Subunits; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D004958:Estradiol