β1-subunit-induced structural rearrangements of the Ca2+- and voltage-activated K+ (BK) channel

Large-conductance Ca2+- and voltage-activated K+ (BK) channels are involved in a large variety of physiological processes. Regulatory beta-subunits are one of the mechanisms responsible for creating BK channel diversity fundamental to the adequate function of many tissues. However, little is known about the structure of its voltage sensor domain. Here, we present the external architectural details of BK channels using lanthanide-based resonance energy transfer (LRET). We used a genetically encoded lanthanide-binding tag (LBT) to bind terbium as a LRET donor and a fluorophore-labeled iberiotoxin as the LRET acceptor for measurements of distances within the BK channel structure in a living cell. By introducing LBTs in the extracellular region of the alpha- or beta 1-subunit, we determined (i) a basic extracellular map of the BK channel, (ii) beta 1-subunit-induced rearrangements of the voltage sensor in alpha-subunits, and (iii) the relative position of the beta 1-subunit within the alpha/beta 1-subunit complex.