The NHR1-1 of Prs1 and the Pentameric Motif 284KKCPK288 of Prs3 Permit Multi-functionality of the PRPP Synthetase in Saccharomyces Cerevisiae

Overview

Journal FEMS Yeast Res

Publisher Oxford University Press

Specialty Microbiology

Date 2019 Jan 17

PMID 30649305

Citations 2

Authors

Maelle Sauvaget

Fraser Hutton

Robert Coull

Stefano Vavassori

Ke Wang

Aleksandra Reznik

Tatsiana Chyker

Chelsea G Newfield

Eloise Euston

Gerrit Benary

Lilian M Schweizer

Michael Schweizer

Affiliations

Soon will be listed here.

Abstract

The five-membered PRS gene family of Saccharomyces cerevisiae is an example of gene duplication allowing the acquisition of novel functions. Each of the five Prs polypeptides is theoretically capable of synthesising PRPP but at least one of the following heterodimers is required for survival: Prs1/Prs3, Prs2/Prs5 and Prs4/Prs5. Prs3 contains a pentameric motif 284KKCPK288 found only in nuclear proteins. Deletion of 284KKCPK288 destabilises the Prs1/Prs3 complex resulting in a cascade of events, including reduction in PRPP synthetase activity and altered cell wall integrity (CWI) as measured by caffeine sensitivity and Rlm1 expression. Prs3 also interacts with the kinetochore-associated protein, Nuf2. Following the possibility of 284KKCPK288-mediated transport of the Prs1/Prs3 complex to the nucleus, it may interact with Nuf2 and phosphorylated Slt2 permitting activation of Rlm1. This scenario explains the breakdown of CWI encountered in mutants lacking PRS3 or deleted for 284KKCPK288. However, removal of NHR1-1 from Prs1 does not disrupt the Prs1/Prs3 interaction as shown by increased PRPP synthetase activity. This is evidence for the separation of the two metabolic functions of the PRPP-synthesising machinery: provision of PRPP and maintenance of CWI and is an example of evolutionary development when multiple copies of a gene were present in the ancestral organism.

Citing Articles

Hypothesis: evidence that the PRS gene products of Saccharomyces cerevisiae support both PRPP synthesis and maintenance of cell wall integrity.

Murdoch E, Schweizer L, Schweizer M Curr Genet. 2024; 70(1):6.

PMID: 38733432 PMC: 11088543. DOI: 10.1007/s00294-024-01290-w.

Contribution of Model Organisms to Investigating the Far-Reaching Consequences of PRPP Metabolism on Human Health and Well-Being.

Ugbogu E, Schweizer L, Schweizer M Cells. 2022; 11(12).

PMID: 35741038 PMC: 9221600. DOI: 10.3390/cells11121909.

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