Mutations and deletions within the S8-S9 interdomain region abolish complementation of N- and C-terminal domains of Ca(2+)-activated K+ (BK) channels.

A full length alpha-subunit of the Ca(2+)-activated K+ (BK) channel with an inactivating mutation in the C-terminus can complement a functional C-terminal fragment. We analyzed deletions and amino acid changes within the S8-S9 interdomain region for their ability to allow complementation. Cys612 and His616 that are located in a region that contains two overlapping signature sequences, a immunoglobulin signature sequence and a heme binding domain, are essential for a functional channel. These two amino acid residues are also essential for complementation. The deletion of the PEST sequence does not affect the function of the BK channel; however, without the PEST sequence, complementation by a functional C-terminal fragments is no longer possible. The ability to complement a functional channel is restricted to the C-terminal fragment and requires that the complete alpha-subunit or the larger N-terminal fragment contains both, the immunoglobulin signature sequence the PEST sequence.