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

Amparo Ruiz, Asier González, Ivan Muñoz, Raquel Serrano, J. Albert Abrie, Erick Strauss, Joaquín Ariño

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)


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 candidatesg-Ykl088w, Hal3 and Vhs3g-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. © 2009 Nature America, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)920-928
JournalNature Chemical Biology
Publication statusPublished - 1 Jan 2009


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