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

doi:10.1038/nchembio.243

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

Nat Chem Biol. 2009 Dec;5(12):920-8. doi: 10.1038/nchembio.243. Epub 2009 Nov 1.

Authors

Amparo Ruiz¹, Asier González, Ivan Muñoz, Raquel Serrano, J Albert Abrie, Erick Strauss, Joaquín Ariño

Affiliation

¹ Departament de Bioquimica i Biologia Molecular, Universitat Autònoma de Barcelona, Spain.

PMID: 19915539
DOI: 10.1038/nchembio.243

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Carboxy-Lyases / genetics
Carboxy-Lyases / metabolism*
Carboxy-Lyases / physiology
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Cycle Proteins / physiology
Coenzyme A / biosynthesis*
Crystallography, X-Ray
Models, Molecular
Molecular Sequence Data
Phosphoprotein Phosphatases / genetics
Phosphoprotein Phosphatases / metabolism*
Phosphoprotein Phosphatases / physiology
Protein Binding
Saccharomyces cerevisiae / enzymology
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Saccharomyces cerevisiae Proteins / physiology

Substances

Cell Cycle Proteins
SIS2 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
PPZ1 protein, S cerevisiae
Phosphoprotein Phosphatases
VHS3 protein, S cerevisiae
Carboxy-Lyases
Phosphopantothenoyl-cysteine decarboxylase
Coenzyme A

Associated data

PubChem-Substance/85247938
PubChem-Substance/85247939
PubChem-Substance/85247940
PubChem-Substance/85247941
PubChem-Substance/85247942
PubChem-Substance/85247943
PubChem-Substance/85247944
PubChem-Substance/85247945
PubChem-Substance/85247946
PubChem-Substance/85247947
PubChem-Substance/85247948