Fig. 8. Model for the sequence of events leading to the functional inactivation of the eight Arg-based signals present in the K_ATP-channel complex. The shapes illustrating the Kir6.2 tetramer (Antcliff et al., 2005), the heterooctameric K_ATP-channel complex (Mikhailov et al., 2005), or the 14-3-3 dimer (Petosa et al., 1998; Yaffe et al., 1997) are based on homology models or structural analysis by single-particle electron microscopy or X-ray crystallography. They are shown to scale in order to indicate the relative sizes. As 14-3-3-binding sites other than the one provided by the distal tail of Kir6.2 remain unknown, the position of the 14-3-3 dimer is entirely hypothetical. Filled circles with white Rs represent active Arg-based ER-localization signals, open circles symbolize inactiviation of the signal. (A) The Arg-based signal of SUR1 could be inactivated by direct binding of 14-3-3 to this region of the protein (masking). (B) The Arg-based signal of SUR1 could be indirectly inactivated by 14-3-3 recruitment to a binding site in the vicinity of the distal tail of Kir6.2.