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A mechanism for CO regulation of ion channels

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 t...

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Detalles Bibliográficos
Autores principales: Kapetanaki, Sofia M., Burton, Mark J., Basran, Jaswir, Uragami, Chiasa, Moody, Peter C. E., Mitcheson, John S., Schmid, Ralf, Davies, Noel W., Dorlet, Pierre, Vos, Marten H., Storey, Nina M., Raven, Emma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834611/
https://www.ncbi.nlm.nih.gov/pubmed/29500353
http://dx.doi.org/10.1038/s41467-018-03291-z
Descripción
Sumario: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 K(ATP) channels. We find that CO activates K(ATP) channels and that heme binding to a CXXHX(16)H 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.