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 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.
models deposited to PDB as: 7RL0,7RNR,7RKH,7RL5,7RNL,7RMF,7RMK,7RMC,7RMO,7RMVmaps deposited to EMDB as: EMD-24512,EMD-24581,EMD-24497,EMD-24516,EMD-24579,EMD-24566,EMD-24575,EMD-24560,EMD-24576,EMD-24578
Article and author information
National Institutes of Health (R01 grant,GM118396)
- Justin M Kollman
National Institutes of Health (Graduate Student Training Grant,T32 GM007270)
- Jesse M Hansen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Edward H Egelman, University of Virginia, United States
- Preprint posted: August 26, 2021 (view preprint)
- Received: August 26, 2021
- Accepted: November 3, 2021
- Accepted Manuscript published: November 4, 2021 (version 1)
- Version of Record published: December 2, 2021 (version 2)
© 2021, Hansen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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