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Title: A heme-binding domain controls regulation of ATP-dependent potassium channels
Authors: Burton, Mark J.
Kapetanaki, Sophia M.
Chernova, Tatyana
Jamieson, Andrew G.
Dorlet, Pierre
Santolini, Jérôme
Moody, Peter C. E.
Mitcheson, John S.
Davies, Noel W.
Schmid, Ralf
Raven, Emma L.
Storey, Nina M.
First Published: 5-Apr-2016
Publisher: National Academy of Sciences
Citation: Proceedings of the National Academy of Sciences, 2016, 113 (14), pp. 3785-3790
Abstract: Heme iron has many and varied roles in biology. Most commonly it binds as a prosthetic group to proteins, and it has been widely supposed and amply demonstrated that subtle variations in the protein structure around the heme, including the heme ligands, are used to control the reactivity of the metal ion. However, the role of heme in biology now appears to also include a regulatory responsibility in the cell; this includes regulation of ion channel function. In this work, we show that cardiac KATP channels are regulated by heme. We identify a cytoplasmic heme-binding CXXHX16H motif on the sulphonylurea receptor subunit of the channel, and mutagenesis together with quantitative and spectroscopic analyses of heme-binding and single channel experiments identified Cys628 and His648 as important for heme binding. We discuss the wider implications of these findings and we use the information to present hypotheses for mechanisms of heme-dependent regulation across other ion channels.
DOI Link: 10.1073/pnas.1600211113
eISSN: 1091-6490
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © National Academy of Sciences 2016. Deposited with reference to the publisher’s archiving policy available on the SHERPA/RoMEO website.
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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