Higher order assemblies in the GET membrane protein-targeting pathway

Abstract

Tail-anchor (TA) proteins represent an important and diverse class of membrane proteins that are unable to be targeted via the co-translational SRP pathway. Instead, recent discoveries have identified factors directly involved in targeting these proteins to the ER. In yeast, these proteins form the GET pathway. Our lab has focused on structural and mechanistic studies of these proteins. The pathway as we posit begins with cytoplasmic chaperones that deliver the TA-proteins to Sgt2, which routes the proteins to Get3 via a Get4/Get5 hetero-tetramer. Get3 then forms a stable complex with the TA and delivers the proteins to the ER membrane. We have begun characterizing these complexes using structural biology and biochemistry. I will frame a discussion of the pathway from our unique structural perspective presenting new results on parts of the pathway.