Abstract
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.
Highlights
KirBac3.1 is a prokaryotic homolog of eukaryotic Kir channels
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)
One of the activatory mutations previously identified in the CTD of KirBac3.1 (S205L) is located close to the intersubunit interface between the cytoplasmic domains, and recent studies have implicated an important role for these interfaces in the gating of both prokaryotic and eukaryotic Kir channels [4, 5]
Summary
KirBac3.1 is a prokaryotic homolog of eukaryotic Kir channels. Results: A high-resolution crystal structure of a mutant channel reveals a novel open conformation. 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 alter the electrostatic potential of the inner cytoplasmic cavity. One of the activatory mutations previously identified in the CTD of KirBac3.1 (S205L) is located close to the intersubunit interface between the cytoplasmic domains, and recent studies have implicated an important role for these interfaces in the gating of both prokaryotic and eukaryotic Kir channels [4, 5]. We present the crystal structure of a mutant KirBac3.1 channel at 2.46 Å resolution that shows the effect of the S205L mutation in the context of an open channel, and we have determined the functional and structural consequences of this mutation
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