The NHR1-1 of Prs1 and the pentameric motif 284KKCPK288 of Prs3 permit multi-functionality of the PRPP synthetase in Saccharomyces cerevisiae.

Publisher: Oxford University Press Country of Publication: England NLM ID: 101085384 Publication Model: Print Cited Medium: Internet ISSN: 1567-1364 (Electronic) Linking ISSN: 15671356 NLM ISO Abbreviation: FEMS Yeast Res Subsets: MEDLINE

Publication: 2015- : Oxford Oxford University Press
Original Publication: Amsterdam ; New York : Published by Elsevier Science B.V. on behalf of Federation of European Microbiological Societies, [2001-

Amino Acid Motifs* ; Microbial Viability*; Phosphoribosyl Pyrophosphate/*biosynthesis ; Protein Subunits/*metabolism ; Ribose-Phosphate Pyrophosphokinase/*metabolism ; Saccharomyces cerevisiae/*enzymology ; Saccharomyces cerevisiae/*physiology ; Saccharomyces cerevisiae Proteins/*metabolism; Protein Binding ; Protein Interaction Maps ; Protein Subunits/genetics ; Ribose-Phosphate Pyrophosphokinase/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Sequence Deletion

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.

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United Kingdom Wellcome Trust

0 (Protein Subunits)
0 (Saccharomyces cerevisiae Proteins)
7540-64-9 (Phosphoribosyl Pyrophosphate)
EC 2.7.6.1 (PRS1 protein, S cerevisiae)
EC 2.7.6.1 (PRS3 protein, S cerevisiae)
EC 2.7.6.1 (Ribose-Phosphate Pyrophosphokinase)

Date Created: 20190117 Date Completed: 20190827 Latest Revision: 20200225

20240829

PMC6368438

10.1093/femsyr/foz006

30649305