Isolated Toll-like receptor transmembrane domains are capable of oligomerization.

Toll-like receptors (TLRs) act as the first line of defense against bacterial and viral pathogens by initiating critical defense signals upon dimer activation. The contribution of the transmembrane domain in the dimerization and signaling process has heretofore been overlooked in favor of the extrac...

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Autores principales:	James I Godfroy, Mohammad Roostan, Yurii S Moroz, Ivan V Korendovych, Hang Yin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3f653181de0245099e5514ab555c08ef
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spelling	oai:doaj.org-article:3f653181de0245099e5514ab555c08ef2021-11-18T08:08:52ZIsolated Toll-like receptor transmembrane domains are capable of oligomerization.1932-620310.1371/journal.pone.0048875https://doaj.org/article/3f653181de0245099e5514ab555c08ef2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23155421/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Toll-like receptors (TLRs) act as the first line of defense against bacterial and viral pathogens by initiating critical defense signals upon dimer activation. The contribution of the transmembrane domain in the dimerization and signaling process has heretofore been overlooked in favor of the extracellular and intracellular domains. As mounting evidence suggests that the transmembrane domain is a critical region in several protein families, we hypothesized that this was also the case for Toll-like receptors. Using a combined biochemical and biophysical approach, we investigated the ability of isolated Toll-like receptor transmembrane domains to interact independently of extracellular domain dimerization. Our results showed that the transmembrane domains had a preference for the native dimer partners in bacterial membranes for the entire receptor family. All TLR transmembrane domains showed strong homotypic interaction potential. The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10, but not with TLR4, TLR5, or unrelated transmembrane receptors providing evidence for the specificity of TLR2 transmembrane domain interactions. Peptides for the transmembrane domains of TLR1, TLR2, and TLR6 were synthesized to further study this subfamily of receptors. These peptides validated the heterotypic interactions seen in bacterial membranes and demonstrated that the TLR2 transmembrane domain had moderately strong interactions with both TLR1 and TLR6. Combined, these results suggest a role for the transmembrane domain in Toll-like receptor oligomerization and as such, may be a novel target for further investigation of new therapeutic treatments of Toll-like receptor mediated diseases.James I GodfroyMohammad RoostanYurii S MorozIvan V KorendovychHang YinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e48875 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q James I Godfroy Mohammad Roostan Yurii S Moroz Ivan V Korendovych Hang Yin Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
description	Toll-like receptors (TLRs) act as the first line of defense against bacterial and viral pathogens by initiating critical defense signals upon dimer activation. The contribution of the transmembrane domain in the dimerization and signaling process has heretofore been overlooked in favor of the extracellular and intracellular domains. As mounting evidence suggests that the transmembrane domain is a critical region in several protein families, we hypothesized that this was also the case for Toll-like receptors. Using a combined biochemical and biophysical approach, we investigated the ability of isolated Toll-like receptor transmembrane domains to interact independently of extracellular domain dimerization. Our results showed that the transmembrane domains had a preference for the native dimer partners in bacterial membranes for the entire receptor family. All TLR transmembrane domains showed strong homotypic interaction potential. The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10, but not with TLR4, TLR5, or unrelated transmembrane receptors providing evidence for the specificity of TLR2 transmembrane domain interactions. Peptides for the transmembrane domains of TLR1, TLR2, and TLR6 were synthesized to further study this subfamily of receptors. These peptides validated the heterotypic interactions seen in bacterial membranes and demonstrated that the TLR2 transmembrane domain had moderately strong interactions with both TLR1 and TLR6. Combined, these results suggest a role for the transmembrane domain in Toll-like receptor oligomerization and as such, may be a novel target for further investigation of new therapeutic treatments of Toll-like receptor mediated diseases.
format	article
author	James I Godfroy Mohammad Roostan Yurii S Moroz Ivan V Korendovych Hang Yin
author_facet	James I Godfroy Mohammad Roostan Yurii S Moroz Ivan V Korendovych Hang Yin
author_sort	James I Godfroy
title	Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
title_short	Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
title_full	Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
title_fullStr	Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
title_full_unstemmed	Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
title_sort	isolated toll-like receptor transmembrane domains are capable of oligomerization.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3f653181de0245099e5514ab555c08ef
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Isolated Toll-like receptor transmembrane domains are capable of oligomerization.

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