Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis

Mutations in the hexosamine pathway key enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) improve protein quality control and extend C. elegans lifespan. Here the authors present the crystal structures of full-length human GFAT-1 alone and with bound ligands and perform activity assays...

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Autores principales:	Sabine Ruegenberg, Moritz Horn, Christian Pichlo, Kira Allmeroth, Ulrich Baumann, Martin S. Denzel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/e59e6a5f14a34fdf901be6fbcaf41cc6
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spelling	oai:doaj.org-article:e59e6a5f14a34fdf901be6fbcaf41cc62021-12-02T14:40:38ZLoss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis10.1038/s41467-020-14524-52041-1723https://doaj.org/article/e59e6a5f14a34fdf901be6fbcaf41cc62020-02-01T00:00:00Zhttps://doi.org/10.1038/s41467-020-14524-5https://doaj.org/toc/2041-1723Mutations in the hexosamine pathway key enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) improve protein quality control and extend C. elegans lifespan. Here the authors present the crystal structures of full-length human GFAT-1 alone and with bound ligands and perform activity assays, which show that gain-of-function in the longevity-associated G451E variant is caused by a loss of feedback regulation.Sabine RuegenbergMoritz HornChristian PichloKira AllmerothUlrich BaumannMartin S. DenzelNature PortfolioarticleScienceQENNature Communications, Vol 11, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Sabine Ruegenberg Moritz Horn Christian Pichlo Kira Allmeroth Ulrich Baumann Martin S. Denzel Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
description	Mutations in the hexosamine pathway key enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) improve protein quality control and extend C. elegans lifespan. Here the authors present the crystal structures of full-length human GFAT-1 alone and with bound ligands and perform activity assays, which show that gain-of-function in the longevity-associated G451E variant is caused by a loss of feedback regulation.
format	article
author	Sabine Ruegenberg Moritz Horn Christian Pichlo Kira Allmeroth Ulrich Baumann Martin S. Denzel
author_facet	Sabine Ruegenberg Moritz Horn Christian Pichlo Kira Allmeroth Ulrich Baumann Martin S. Denzel
author_sort	Sabine Ruegenberg
title	Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
title_short	Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
title_full	Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
title_fullStr	Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
title_full_unstemmed	Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
title_sort	loss of gfat-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e59e6a5f14a34fdf901be6fbcaf41cc6
work_keys_str_mv	AT sabineruegenberg lossofgfat1feedbackregulationactivatesthehexosaminepathwaythatmodulatesproteinhomeostasis AT moritzhorn lossofgfat1feedbackregulationactivatesthehexosaminepathwaythatmodulatesproteinhomeostasis AT christianpichlo lossofgfat1feedbackregulationactivatesthehexosaminepathwaythatmodulatesproteinhomeostasis AT kiraallmeroth lossofgfat1feedbackregulationactivatesthehexosaminepathwaythatmodulatesproteinhomeostasis AT ulrichbaumann lossofgfat1feedbackregulationactivatesthehexosaminepathwaythatmodulatesproteinhomeostasis AT martinsdenzel lossofgfat1feedbackregulationactivatesthehexosaminepathwaythatmodulatesproteinhomeostasis
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Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis

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