A heme-binding domain controls regulation of ATP-dependent potassium channels

Mark J. Burton, Sofia M. Kapetanaki, Tatyana Chernova, Andrew G. Jamieson, Pierre Dorlet, Jérôme Santolini, Peter C.E. Moody, John S. Mitcheson, Noel W. Davies, Ralf Schmid, Emma L. Raven*, Nina M. Storey

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3785-3790
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number14
DOIs
Publication statusPublished - 5 Apr 2016

Keywords

  • Heme
  • Heme regulation
  • K channel
  • Potassium channel
  • SUR2A

Fingerprint Dive into the research topics of 'A heme-binding domain controls regulation of ATP-dependent potassium channels'. Together they form a unique fingerprint.

Cite this