Figure 3. Organization of the HMG-CoA reductase protein.
The integral ER membrane protein HMGR in both mammals and yeast consists of an 8-spanning N-terminal membrane anchor, embedded in the ER membrane (grey) as shown, attached by a linker to the highly conserved catalytic domain that performs the essential enzyme action. Regulated degradation requires the N-terminal transmembrane domain. This region has the conserved sterol-sensing domain (SSD) motif distributed between spans 2 to 5, as discussed in the text.