yeast HMG-CoA reductase (Hmg2p) is the rate limiting enzyme in cholesterol synthesis

  • example of physiological regulation of protein abundance via ERAD
  • when cholesterol levels are high, Hmg2p undergoes a lipid-induced structural change so that it resembles a misfolded protein --> targeted for destruction (Shearer et al., 2005; EMBO J). Thus when Hmg2p is not needed, it is constitutively degraded
  • direct recognition of Hmg2p by Hrd1p circumvents the need for many known Hrd1p adaptor proteins, including Der1p, Usa1p and Yos9p