Year: 2019
Type: dissertation
Abstract: The Orm family of proteins are conserved throughout eukaryotes and serve as negative regulators of de novo sphingolipid biosynthesis. Orm proteins are integral endoplasmic reticulum membrane proteins that associate with serine palmitoyltransferase, which catalyzes the first committed step of sphingolipid biosynthesis. Mammalian genomes encode three Orm paralogs, ORMDL1, ORMDL2 and ORMDL3, while yeast express two paralogs, ORM1 and ORM2. The ORMs contain four transmembrane domains with both N and C-termini in the cytosol but beyond this little is known about their structure. To better understand the function of Orm proteins I performed targeted mutagenesis of the yeast ORM1, focusing on the highly conserved cytosolic loop. Specifically, deletion of the invariant WEQ148-150 residues results in an apparent reduction in function. This is not attributable to a defect in Orm1ΔWEQ protein localization, nor to its ability to interact with serine palmitoyltransferase. I hypothesize that this region may be critical for detecting ceramide.
Source: TSpace (University of Toronto)
Author: Omar Mourad
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3013065798