Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism

Abstract Toll-like receptors (TLRs) play a key role in the innate and adaptive immune systems. While a lot of structural data is available for the extracellular and cytoplasmic domains of TLRs, and a model of the dimeric full-length TLR3 receptor in the active state was build, the conformation of th...

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Autores principales:	Konstantin S. Mineev, Sergey A. Goncharuk, Marina V. Goncharuk, Pavel E. Volynsky, Ekaterina V. Novikova, Alexander S. Aresinev
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dea916c8e3f84fe9aa8fca25b00f37a1
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spelling	oai:doaj.org-article:dea916c8e3f84fe9aa8fca25b00f37a12021-12-02T16:06:22ZSpatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism10.1038/s41598-017-07250-42045-2322https://doaj.org/article/dea916c8e3f84fe9aa8fca25b00f37a12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07250-4https://doaj.org/toc/2045-2322Abstract Toll-like receptors (TLRs) play a key role in the innate and adaptive immune systems. While a lot of structural data is available for the extracellular and cytoplasmic domains of TLRs, and a model of the dimeric full-length TLR3 receptor in the active state was build, the conformation of the transmembrane (TM) domain and juxtamembrane regions in TLR dimers is still unclear. In the present work, we study the transmembrane and juxtamembrane parts of human TLR4 receptor using solution NMR spectroscopy in a variety of membrane mimetics, including phospholipid bicelles. We show that the juxtamembrane hydrophobic region of TLR4 includes a part of long TM α-helix. We report the dimerization interface of the TM domain and claim that long TM domains with transmembrane charged aminoacids is a common feature of human toll-like receptors. This fact is analyzed from the viewpoint of protein activation mechanism, and a model of full-length TLR4 receptor in the dimeric state has been proposed.Konstantin S. MineevSergey A. GoncharukMarina V. GoncharukPavel E. VolynskyEkaterina V. NovikovaAlexander S. AresinevNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Konstantin S. Mineev Sergey A. Goncharuk Marina V. Goncharuk Pavel E. Volynsky Ekaterina V. Novikova Alexander S. Aresinev Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism
description	Abstract Toll-like receptors (TLRs) play a key role in the innate and adaptive immune systems. While a lot of structural data is available for the extracellular and cytoplasmic domains of TLRs, and a model of the dimeric full-length TLR3 receptor in the active state was build, the conformation of the transmembrane (TM) domain and juxtamembrane regions in TLR dimers is still unclear. In the present work, we study the transmembrane and juxtamembrane parts of human TLR4 receptor using solution NMR spectroscopy in a variety of membrane mimetics, including phospholipid bicelles. We show that the juxtamembrane hydrophobic region of TLR4 includes a part of long TM α-helix. We report the dimerization interface of the TM domain and claim that long TM domains with transmembrane charged aminoacids is a common feature of human toll-like receptors. This fact is analyzed from the viewpoint of protein activation mechanism, and a model of full-length TLR4 receptor in the dimeric state has been proposed.
format	article
author	Konstantin S. Mineev Sergey A. Goncharuk Marina V. Goncharuk Pavel E. Volynsky Ekaterina V. Novikova Alexander S. Aresinev
author_facet	Konstantin S. Mineev Sergey A. Goncharuk Marina V. Goncharuk Pavel E. Volynsky Ekaterina V. Novikova Alexander S. Aresinev
author_sort	Konstantin S. Mineev
title	Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism
title_short	Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism
title_full	Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism
title_fullStr	Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism
title_full_unstemmed	Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism
title_sort	spatial structure of tlr4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/dea916c8e3f84fe9aa8fca25b00f37a1
work_keys_str_mv	AT konstantinsmineev spatialstructureoftlr4transmembranedomaininbicellesprovidestheinsightintothereceptoractivationmechanism AT sergeyagoncharuk spatialstructureoftlr4transmembranedomaininbicellesprovidestheinsightintothereceptoractivationmechanism AT marinavgoncharuk spatialstructureoftlr4transmembranedomaininbicellesprovidestheinsightintothereceptoractivationmechanism AT pavelevolynsky spatialstructureoftlr4transmembranedomaininbicellesprovidestheinsightintothereceptoractivationmechanism AT ekaterinavnovikova spatialstructureoftlr4transmembranedomaininbicellesprovidestheinsightintothereceptoractivationmechanism AT alexandersaresinev spatialstructureoftlr4transmembranedomaininbicellesprovidestheinsightintothereceptoractivationmechanism
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Spatial structure of TLR4 transmembrane domain in bicelles provides the insight into the receptor activation mechanism

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