Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC306
X-ray crystal structure of a prokaryotic inwardly-rectifying (KirBac) potassium channel reveals the mechanism of channel opening at the bundle-crossing gate.
V. N. Bavro1, R. De Zorzi2, C. Venien-Bryan2, S. J. Tucker1
1. Dept Physics, University of Oxford, Oxford, United Kingdom. 2. Dept Biochemistry, University of Oxford, Oxford, United Kingdom.
Inwardly-rectifying (Kir) potassium channels are important regulators of cellular electrical activity and excitability and inherited mutations in these channels underlie a wide range of channelopathies. Yet despite the wealth of high-resolution structural information which now exists for this class of K+ channels, the mechanism by which they open and close, and how this process is regulated are still not fully understood. The primary gating mechanism is thought to involve opening and closure of the conductive pathway at the cytoplasmic bundle crossing. However, all of the available crystal structures of either eukaryotic Kir or prokaryotic KirBac channels are fully closed at the bundle crossing gate and there are currently no available structures of a Kir channel with the bundle-crossing in an open conformation. In a previous genetic complementation study we identified a range of gating mutations in a prokaryotic KirBac channel and we have now used these mutants to help determine the X-ray crystal structure of a KirBac channel at 3.05Å resolution. This novel structure reveals a channel with the transmembrane helices in an open conformation as well as highlighting a number of important interactions between the cytoplasmic assembly and the transmembrane helices that are likely to be essential for maintaining the channel in the open state. This structure therefore provides an important structural insight into the mechanism of Kir channel gating and our understanding of how this process can be regulated by physiological ligands.
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