Moonlighting proteins in yeasts

Abstract

Proteins able to participate in unrelated biological processes have been grouped under the generic name of moonlighting proteins. Work with different yeast species has uncovered a great number of moonlighting proteins and shown their importance for adequate functioning of the yeast cell. Moonlighting activities in yeasts include such diverse functions as control of gene expression, organelle assembly, and modification of the activity of metabolic pathways. In this review, we consider several well-studied moonlighting proteins in different yeast species, paying attention to the experimental approaches used to identify them and the evidence that supports their participation in the unexpected function. Usually, moonlighting activities have been uncovered unexpectedly, and up to now, no satisfactory way to predict moonlighting activities has been found. Among the well-characterized moonlighting proteins in yeasts, enzymes from the glycolytic pathway appear to be prominent. For some cases, it is shown that despite close phylogenetic relationships, moonlighting activities are not necessarily conserved among yeast species. Organisms may utilize moonlighting to add a new layer of regulation to conventional regulatory networks. The existence of this type of proteins in yeasts should be taken into account when designing mutant screens or in attempts to model or modify yeast metabolism.

FIG. 1.

Simplified scheme of the role of Hxk2 in catabolite repression. In the presence of high glucose, a fraction of Hxk2 enters the nucleus and binds to the repressor protein Mig1. Hxk2 hinders the phosphorylation of Mig1 by any active Snf1 that may be present and allows Mig1 to exert its repressive effect. Hxk2 also interacts with Reg1, and this interaction facilitates the action of the phosphatase Glc7 on Snf1 to maintain it in its inactive, dephosphorylated form; this, in turn, contributes to a low level of phosphorylation of Mig1. In the absence of glucose, Snf1 is phosphorylated by any of the kinases Elm1, Tos3, and Sak1; in this form, it phosphorylates Mig1, thus maintaining it and Hxk2 in the cytosol. For the sake of simplicity, other proteins that form complexes with Snf1, Mig1, or Hxk2 are not represented.

FIG. 2.

Moonlighting activities related to arginine metabolism. (a) Scheme of inositol polyphosphate biosynthesis. Arg82 was initially identified as a protein that participates in the regulation of the transcription of genes related to arginine metabolism (13). Further studies have shown that it also functions as an Ins(1,4,5)P₃ and Ins(1,3,4,5)P₄ kinase (106, 123). (b) Scheme of arginine biosynthesis and degradation. Ornithine is a common metabolite that participates in both processes. See the text for details. OTCase, ornithine transcarbamylase.