Cargando…

Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis

Transmembrane signaling proteins play a crucial role in the transduction of information across cell membranes. One function of regulated intramembrane proteolysis (RIP) is the release of signaling factors from transmembrane proteins. To study the role of transmembrane domains (TMDs) in modulating st...

Descripción completa

Detalles Bibliográficos
Autores principales: Kupke, Thomas, Klare, Johann P., Brügger, Britta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021776/
https://www.ncbi.nlm.nih.gov/pubmed/32060393
http://dx.doi.org/10.1038/s42003-020-0800-0
_version_ 1783497943871913984
author Kupke, Thomas
Klare, Johann P.
Brügger, Britta
author_facet Kupke, Thomas
Klare, Johann P.
Brügger, Britta
author_sort Kupke, Thomas
collection PubMed
description Transmembrane signaling proteins play a crucial role in the transduction of information across cell membranes. One function of regulated intramembrane proteolysis (RIP) is the release of signaling factors from transmembrane proteins. To study the role of transmembrane domains (TMDs) in modulating structure and activity of released signaling factors, we purified heterologously expressed human transmembrane proteins and their proteolytic processing products from Escherichia coli. Here we show that CD74 and TNFα are heme binding proteins. Heme coordination depends on both a cysteine residue proximal to the membrane and on the oligomerization of the TMD. Furthermore, we show that the various processing products have different modes of heme coordination. We suggest that RIP changes the mode of heme binding of these proteins and generates heme binding peptides with yet unexplored functions. The identification of a RIP modulated cofactor binding of transmembrane signaling proteins sheds new light on the regulation of cell signaling pathways.
format Online
Article
Text
id pubmed-7021776
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-70217762020-03-03 Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis Kupke, Thomas Klare, Johann P. Brügger, Britta Commun Biol Article Transmembrane signaling proteins play a crucial role in the transduction of information across cell membranes. One function of regulated intramembrane proteolysis (RIP) is the release of signaling factors from transmembrane proteins. To study the role of transmembrane domains (TMDs) in modulating structure and activity of released signaling factors, we purified heterologously expressed human transmembrane proteins and their proteolytic processing products from Escherichia coli. Here we show that CD74 and TNFα are heme binding proteins. Heme coordination depends on both a cysteine residue proximal to the membrane and on the oligomerization of the TMD. Furthermore, we show that the various processing products have different modes of heme coordination. We suggest that RIP changes the mode of heme binding of these proteins and generates heme binding peptides with yet unexplored functions. The identification of a RIP modulated cofactor binding of transmembrane signaling proteins sheds new light on the regulation of cell signaling pathways. Nature Publishing Group UK 2020-02-14 /pmc/articles/PMC7021776/ /pubmed/32060393 http://dx.doi.org/10.1038/s42003-020-0800-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kupke, Thomas
Klare, Johann P.
Brügger, Britta
Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
title Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
title_full Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
title_fullStr Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
title_full_unstemmed Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
title_short Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
title_sort heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021776/
https://www.ncbi.nlm.nih.gov/pubmed/32060393
http://dx.doi.org/10.1038/s42003-020-0800-0
work_keys_str_mv AT kupkethomas hemebindingoftransmembranesignalingproteinsundergoingregulatedintramembraneproteolysis
AT klarejohannp hemebindingoftransmembranesignalingproteinsundergoingregulatedintramembraneproteolysis
AT bruggerbritta hemebindingoftransmembranesignalingproteinsundergoingregulatedintramembraneproteolysis