Project 16

Dissecting the role of SND pathway components in ER membrane protein insertion

Principle Investigator: Dr. Melanie McDowell

Research Areas: Structural Biology, Biochemistry, Biophysics

Summary

Most eukaryotic integral membrane proteins (IMPs) must be targeted to and inserted into the endoplasmic reticulum (ER) membrane after their translation by cytosolic ribosomes. As IMPs display a huge diversity in the quantity, relative positioning and biochemical properties of their transmembrane domains (TMDs), they require several distinct pathways for their ER targeting and insertion. Discovered in 2016, the signal recognition particle independent (SND) pathway specifically caters for IMP clients with their first TMD in a central position within the protein sequence, yet also provides an alternative route for more diverse IMP substrates when their canonical pathways are impaired. In Saccharomyces cerevisiae, three components of the SND pathway have been identified: the cytosolic protein Snd1 and the Snd2-Snd3 IMP complex. However, the characterization of the SND pathway is in its infancy, with little known about the interplay between these components and their precise roles. We propose to obtain a molecular-level understanding of the Snd proteins using a multi-faceted structural, biophysical and biochemical approach.