University of Leicester
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A mechanism for CO regulation of ion channels.

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posted on 2018-04-23, 09:50 authored by Sofia M. Kapetanaki, Mark J. Burton, J. Basran, C. Uragami, Peter C. E. Moody, John S. Mitcheson, Ralf Schmid, Noel W. Davies, P. Dorlet, M. H. Vos, Nina M. Storey, Emma Raven
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.



Nature Communications, 2018, 9, 907

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Author Correction: A mechanism for CO regulation of ion channels Nature Communications volume 9, Article number: 3354 (2018) Correction to: Nature Communications; published online 02 March 2018 The originally published version of this article contained an error in the subheading ‘Heme is required for CO-dependent channel activation’, which was incorrectly given as ‘Hame is required for CO-dependent channel activation’. This has now been corrected in both the PDF and HTML versions of the Article.