Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation

Many metabolic enzymes self-assemble into micron-scale filaments to organize and regulate metabolism. The appearance of these assemblies often coincides with large metabolic changes as in development, cancer, and stress. Yeast undergo cytoplasmic acidification upon starvation, triggering the assembl...

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Autores principales:	Jesse M Hansen, Avital Horowitz, Eric M Lynch, Daniel P Farrell, Joel Quispe, Frank DiMaio, Justin M Kollman
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	stress response metabolic filaments enzyme allostery cryo-EM Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e958299121e7450aac97494ed011adbf
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spelling	oai:doaj.org-article:e958299121e7450aac97494ed011adbf2021-12-03T09:05:31ZCryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation10.7554/eLife.733682050-084Xe73368https://doaj.org/article/e958299121e7450aac97494ed011adbf2021-11-01T00:00:00Zhttps://elifesciences.org/articles/73368https://doaj.org/toc/2050-084XMany metabolic enzymes self-assemble into micron-scale filaments to organize and regulate metabolism. The appearance of these assemblies often coincides with large metabolic changes as in development, cancer, and stress. Yeast undergo cytoplasmic acidification upon starvation, triggering the assembly of many metabolic enzymes into filaments. However, it is unclear how these filaments assemble at the molecular level and what their role is in the yeast starvation response. CTP Synthase (CTPS) assembles into metabolic filaments across many species. Here, we characterize in vitro polymerization and investigate in vivo consequences of CTPS assembly in yeast. Cryo-EM structures reveal a pH-sensitive assembly mechanism and highly ordered filament bundles that stabilize an inactive state of the enzyme, features unique to yeast CTPS. Disruption of filaments in cells with non-assembly or pH-insensitive mutations decreases growth rate, reflecting the importance of regulated CTPS filament assembly in homeotstasis.Jesse M HansenAvital HorowitzEric M LynchDaniel P FarrellJoel QuispeFrank DiMaioJustin M KollmaneLife Sciences Publications Ltdarticlestress responsemetabolic filamentsenzyme allosterycryo-EMMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	stress response metabolic filaments enzyme allostery cryo-EM Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	stress response metabolic filaments enzyme allostery cryo-EM Medicine R Science Q Biology (General) QH301-705.5 Jesse M Hansen Avital Horowitz Eric M Lynch Daniel P Farrell Joel Quispe Frank DiMaio Justin M Kollman Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation
description	Many metabolic enzymes self-assemble into micron-scale filaments to organize and regulate metabolism. The appearance of these assemblies often coincides with large metabolic changes as in development, cancer, and stress. Yeast undergo cytoplasmic acidification upon starvation, triggering the assembly of many metabolic enzymes into filaments. However, it is unclear how these filaments assemble at the molecular level and what their role is in the yeast starvation response. CTP Synthase (CTPS) assembles into metabolic filaments across many species. Here, we characterize in vitro polymerization and investigate in vivo consequences of CTPS assembly in yeast. Cryo-EM structures reveal a pH-sensitive assembly mechanism and highly ordered filament bundles that stabilize an inactive state of the enzyme, features unique to yeast CTPS. Disruption of filaments in cells with non-assembly or pH-insensitive mutations decreases growth rate, reflecting the importance of regulated CTPS filament assembly in homeotstasis.
format	article
author	Jesse M Hansen Avital Horowitz Eric M Lynch Daniel P Farrell Joel Quispe Frank DiMaio Justin M Kollman
author_facet	Jesse M Hansen Avital Horowitz Eric M Lynch Daniel P Farrell Joel Quispe Frank DiMaio Justin M Kollman
author_sort	Jesse M Hansen
title	Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation
title_short	Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation
title_full	Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation
title_fullStr	Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation
title_full_unstemmed	Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation
title_sort	cryo-em structures of ctp synthase filaments reveal mechanism of ph-sensitive assembly during budding yeast starvation
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/e958299121e7450aac97494ed011adbf
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Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation

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