Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.

Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein-coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking, endothelial development, integrity, and maturation. We performed five all-atom 700...

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Autores principales:	Shuguang Yuan, Rongliang Wu, Dorota Latek, Bartosz Trzaskowski, Slawomir Filipek
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cbad0f3702544a84924e7a2641c576b6
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spelling	oai:doaj.org-article:cbad0f3702544a84924e7a2641c576b62021-11-18T05:53:33ZLipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.1553-734X1553-735810.1371/journal.pcbi.1003261https://doaj.org/article/cbad0f3702544a84924e7a2641c576b62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098103/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein-coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking, endothelial development, integrity, and maturation. We performed five all-atom 700 ns molecular dynamics simulations of the sphingosine 1-phosphate receptor 1 (S1P₁) based on recently released crystal structure of that receptor with an antagonist. We found that the initial movements of amino acid residues occurred in the area of highly conserved W269⁶·⁴⁸ in TM6 which is close to the ligand binding location. Those residues located in the central part of the receptor and adjacent to kinks of TM helices comprise of a transmission switch. Side chains movements of those residues were coupled to the movements of water molecules inside the receptor which helped in the gradual opening of intracellular part of the receptor. The most stable parts of the protein were helices TM1 and TM2, while the largest movement was observed for TM7, possibly due to the short intracellular part starting with a helix kink at P⁷·⁵⁰, which might be the first helix to move at the intracellular side. We show for the first time the detailed view of the concerted action of the transmission switch and Trp (W⁶·⁴⁸) rotamer toggle switch leading to redirection of water molecules flow in the central part of the receptor. That event is a prerequisite for subsequent changes in intracellular part of the receptor involving water influx and opening of the receptor structure.Shuguang YuanRongliang WuDorota LatekBartosz TrzaskowskiSlawomir FilipekPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 10, p e1003261 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Shuguang Yuan Rongliang Wu Dorota Latek Bartosz Trzaskowski Slawomir Filipek Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
description	Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein-coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking, endothelial development, integrity, and maturation. We performed five all-atom 700 ns molecular dynamics simulations of the sphingosine 1-phosphate receptor 1 (S1P₁) based on recently released crystal structure of that receptor with an antagonist. We found that the initial movements of amino acid residues occurred in the area of highly conserved W269⁶·⁴⁸ in TM6 which is close to the ligand binding location. Those residues located in the central part of the receptor and adjacent to kinks of TM helices comprise of a transmission switch. Side chains movements of those residues were coupled to the movements of water molecules inside the receptor which helped in the gradual opening of intracellular part of the receptor. The most stable parts of the protein were helices TM1 and TM2, while the largest movement was observed for TM7, possibly due to the short intracellular part starting with a helix kink at P⁷·⁵⁰, which might be the first helix to move at the intracellular side. We show for the first time the detailed view of the concerted action of the transmission switch and Trp (W⁶·⁴⁸) rotamer toggle switch leading to redirection of water molecules flow in the central part of the receptor. That event is a prerequisite for subsequent changes in intracellular part of the receptor involving water influx and opening of the receptor structure.
format	article
author	Shuguang Yuan Rongliang Wu Dorota Latek Bartosz Trzaskowski Slawomir Filipek
author_facet	Shuguang Yuan Rongliang Wu Dorota Latek Bartosz Trzaskowski Slawomir Filipek
author_sort	Shuguang Yuan
title	Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
title_short	Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
title_full	Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
title_fullStr	Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
title_full_unstemmed	Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
title_sort	lipid receptor s1p₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/cbad0f3702544a84924e7a2641c576b6
work_keys_str_mv	AT shuguangyuan lipidreceptors1p1activationschemeconcludedfrommicrosecondallatommoleculardynamicssimulations AT rongliangwu lipidreceptors1p1activationschemeconcludedfrommicrosecondallatommoleculardynamicssimulations AT dorotalatek lipidreceptors1p1activationschemeconcludedfrommicrosecondallatommoleculardynamicssimulations AT bartosztrzaskowski lipidreceptors1p1activationschemeconcludedfrommicrosecondallatommoleculardynamicssimulations AT slawomirfilipek lipidreceptors1p1activationschemeconcludedfrommicrosecondallatommoleculardynamicssimulations
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Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.

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