A Portable Site: A Binding Element for 17β-Estradiol Can Be Placed on Any Subunit of a Nicotinic α4β2 Receptor

Endogenous steroids can modulate the activity of transmitter-gated channels by directly interacting with the receptor. 17 beta-Estradiol potentiates activation of neuronal nicotinic alpha 4 beta 2 receptors by interacting with a 4 aa sequence at the extreme C terminus of the alpha 4 subunit, but it is not known whether potentiation requires that the sequence be placed on a specific subunit (e.g., an alpha 4 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 alpha 4 to the beta 2 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 17 beta-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.