SFB 1208 Lecture

Speaker: Melanie McDowell, University of Heidelberg / MPI of Biophysics, Frankfurt

Title: 'Structural insights into tail-anchored membrane protein biogenesis by the GET insertase complex"

Abstract:
After their synthesis by eukaryotic ribosomes, most integral membrane proteins (IMPs) are inserted into the endoplasmic reticulum (ER) membrane. This requires that the hydrophobic transmembrane domains (TMDs) of IMPs are faithfully chaperoned through the aqueous cytosol and polar membrane surface. The huge diversity in the topology and biochemical properties of IMPs necessitates several distinct pathways for their ER targeting and insertion. One such route, the guided entry of tail-anchored proteins (GET) pathway, mediates the post-translational insertion of tail-anchored (TA) proteins, which have a single TMD at their extreme C-terminus. Within this pathway, the Get1/Get2 insertase in the ER membrane captures the TA protein from the Get3 cytosolic chaperone to mediate membrane insertion. To understand the molecular mechanisms associated with this process, we characterised Get1/Get2/Get3 complexes using cryo-electron microscopy, native mass spectrometry and structure-guided mutagenesis (McDowell et al., 2020). These approaches have provided an updated model for TA protein targeting and insertion by the GET pathway.

Host: Alexej Kedrov

Location: HS 6L

Time: 4:30 p.m.