Key result
S205L mutation stabilizes an open KirBac3.1 channel conformation, altering inner cavity electrostatic potential.
The S205L mutation in the cytoplasmic domain of KirBac3.1 channels stabilizes an open conformation, providing structural insights into Kir channel gating.
No immediate clinical impact; leaves open whether S205L gating insights apply to human Kir channels.
KirBac channels are prokaryotic homologs of mammalian inwardly rectifying potassium (Kir) channels, and recent structures of KirBac3.1 have provided important insights into the structural basis of gating in Kir channels. In this study, we demonstrate that KirBac3.1 channel activity is strongly pH-dependent, and we used x-ray crystallography to determine the structural changes that arise from an activatory mutation (S205L) located in the cytoplasmic domain (CTD). This mutation stabilizes a novel energetically favorable open conformation in which changes at the intersubunit interface in the CTD also alter the electrostatic potential of the inner cytoplasmic cavity. These results provide a structural explanation for the activatory effect of this mutation and provide a greater insight into the role of the CTD in Kir channel gating.
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Zubcevic et al. (2013) studied this question. S205L mutation was evaluated on Structural changes and channel activity. The S205L mutation in the cytoplasmic domain stabilizes an energetically favorable open conformation of the KirBac3.1 channel, altering the electrostatic potential of the inner cytoplasmic cavity.
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