Moonlighting proteins Hal3 and Vhs3 form a heteromeric PPCDC with Ykl088w in yeast CoA biosynthesis.

Nature Chemical Biology
Amparo RuizJoaquín Ariño

Abstract

Unlike most other organisms, the essential five-step coenzyme A biosynthetic pathway has not been fully resolved in yeast. Specifically, the genes encoding the phosphopantothenoylcysteine decarboxylase (PPCDC) activity still remain unidentified. Sequence homology analyses suggest three candidates-Ykl088w, Hal3 and Vhs3-as putative PPCDC enzymes in Saccharomyces cerevisiae. Notably, Hal3 and Vhs3 have been characterized as negative regulatory subunits of the Ppz1 protein phosphatase. Here we show that YKL088w does not encode a third Ppz1 regulatory subunit, and that the essential roles of Ykl088w and the Hal3 and Vhs3 pair are complementary, cannot be interchanged and can be attributed to PPCDC-related functions. We demonstrate that while known eukaryotic PPCDCs are homotrimers, the active yeast enzyme is a heterotrimer that consists of Ykl088w and Hal3/Vhs3 monomers that separately provides two essential catalytic residues. Our results unveil Hal3 and Vhs3 as moonlighting proteins involved in both CoA biosynthesis and protein phosphatase regulation.

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Citations

Nov 17, 2009·Nature Chemical Biology·Andrei L Osterman
Mar 4, 2010·Microbiology and Molecular Biology Reviews : MMBR·Joaquín AriñoHana Sychrová
May 2, 2014·World Journal of Microbiology & Biotechnology·T PaalmeI Nisamedtinov
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Feb 1, 2012·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Xiao-Fei ZhangXiao-Xin Li
Nov 27, 2014·Molecular Microbiology·David CanadellJoaquín Ariño
Nov 30, 2011·The Biochemical Journal·J Albert AbrieJoaquín Ariño
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Aug 8, 2019·International Journal of Molecular Sciences·Chunyi ZhangJoaquín Ariño
Sep 26, 2020·Scientific Reports·Diego VelázquezJoaquín Ariño
Oct 23, 2020·International Journal of Molecular Sciences·Carlos CalafíJoaquín Ariño
Jan 10, 2021·Nature Communications·Vitor MendesTom L Blundell
Jan 28, 2021·International Journal of Molecular Sciences·Jovana BakovićIvan Gout
Apr 28, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Carlos CalafíAntonio Casamayor

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