Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex

Abstract

Previously, a microarray expression study in the yeast Saccharomyces cerevisiae indicated that the ERG28 gene was strongly coregulated with ergosterol biosynthesis. Subsequently, Erg28p was shown to function as an endoplasmic reticulum transmembrane protein, acting as a scaffold to tether the C-4 demethylation enzymatic complex and also to interact with a downstream enzyme, Erg6p. To understand all possible protein interactions involving Erg28p in sterol biosynthesis, a yeast two-hybrid system designed to assess interactions between membrane proteins was used. The Erg28p fusion protein was used as bait to assess interactions with all 14 sterol biosynthetic proteins in a pairwise study based on two reporter systems as well as Western blots demonstrating the release of a transcription factor. Our results indicated that Erg28p not only interacted with the C-4 demethylation enzymes and Erg6p but also with

Effects of Culture Conditions on Ergosterol Biosynthesis bySaccharomyces cerevisiae

“…Nine genes involved in ergosterol biosynthesis were expressed more strongly in S. cerevisiae K-9 than in X2180-1A. Especially, overexpression of HMG1, which encodes HMG CoA reductase and is involved in the main bottleneck of the early ergosterol pathway, 19) and ERG28, which encodes a key protein in the yeast sterol biosynthetic enzyme complex, 20) appear to be related to the higher total ergosterol contents of K-9 than of X2180-1. This might result in the greater ethanol tolerance of K-9 than of X2180-1A.…”

Malformation syndromes caused by disorders of cholesterol synthesis

“…HSD17B7 also participates in the conversion of estrone to estradiol in steroidogenesis ( 282,283 ). In S. cerevisiae , the ERG28 gene encodes a regulatory protein for the complex that may function as a scaffold and tether multiple cholesterologenic enzymes to ER membranes (284)(285)(286). Mammalian orthologs of ERG28 have been identifi ed (284)(285)(286), including the anonymous murine gene Orf11 (NM_021446).…”

“…In S. cerevisiae , the ERG28 gene encodes a regulatory protein for the complex that may function as a scaffold and tether multiple cholesterologenic enzymes to ER membranes (284)(285)(286). Mammalian orthologs of ERG28 have been identifi ed (284)(285)(286), including the anonymous murine gene Orf11 (NM_021446). The Orf11 gene is coordinately upregulated with Sc4mol and Hsd17b7 and other genes involved in cholesterol biosynthesis in Nsdhl defi cient cultured skin fi broblasts ( 287 ), providing circumstantial evidence for its role in mammalian sterol metabolism.…”

Protein–Protein and Protein–Membrane Associations in the Lignin Pathway

“…A small transmembrane protein Erg28p was reported to interact with several enzymes involved in sterol biosynthesis, including CYP51 (or Erg11p), catalyzing sterol 14a-demethylation, and the homolog of plant SMT2 sterol C-24 methyltransferase, in yeast. The Erg28p protein with no reported catalytic activity was proposed to tether a large complex of yeast sterol biosynthetic enzymes (Mo and Bard, 2005). No plant homolog to Erg28p has been reported so far, but several of the proteins identified by TAP might play a role similar to Erg28p and attempts to reveal protein complexes using blue native gel blots of microsomes isolated from plant leaves transfected with CYP98A3 revealed the presence of the CYP98A3 protein in several protein aggregates with molecular masses ranging up to 700 kD (see Supplemental Figure 3 online), which seems to confirm tight association with other membrane proteins.…”

“…SMT2 expression impacts sterol composition of the membrane (Schaeffer et al, 2001) and is associated with vascular patterning (Carland et al, 2002). Erg6p, the yeast homolog of SMT2, has been shown to belong to an ER complex of sterol biosynthetic enzymes in Saccharomyces cerevisiae (Mo et al, 2004;Mo and Bard, 2005).…”