A mechanism for CO regulation of ion channels

Sofia M. Kapetanaki, Mark J. Burton, Jaswir Basran, Chiasa Uragami, Peter C. E. Moody, John S. Mitcheson, Ralf Schmid, Noel W. Davies, Pierre Dorlet, Marten H. Vos, Nina M. Storey () and Emma Raven ()
Additional contact information
Sofia M. Kapetanaki: University of Leicester
Mark J. Burton: University of Leicester
Jaswir Basran: University of Leicester
Chiasa Uragami: Univ. Paris-Sud, Université Paris-Saclay
Peter C. E. Moody: University of Leicester
John S. Mitcheson: University of Leicester
Ralf Schmid: University of Leicester
Noel W. Davies: University of Leicester
Pierre Dorlet: Univ. Paris-Sud, Université Paris-Saclay
Marten H. Vos: Université Paris-Saclay
Nina M. Storey: University of Leicester
Emma Raven: University of Leicester

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Despite being highly toxic, carbon monoxide (CO) is also an essential intracellular signalling molecule. The mechanisms of CO-dependent cell signalling are poorly defined, but are likely to involve interactions with heme proteins. One such role for CO is in ion channel regulation. Here, we examine the interaction of CO with KATP channels. We find that CO activates KATP channels and that heme binding to a CXXHX16H motif on the SUR2A receptor is required for the CO-dependent increase in channel activity. Spectroscopic and kinetic data were used to quantify the interaction of CO with the ferrous heme-SUR2A complex. The results are significant because they directly connect CO-dependent regulation to a heme-binding event on the channel. We use this information to present molecular-level insight into the dynamic processes that control the interactions of CO with a heme-regulated channel protein, and we present a structural framework for understanding the complex interplay between heme and CO in ion channel regulation.

Date: 2018
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DOI: 10.1038/s41467-018-03291-z

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