A detailed look at tail-anchored membrane protein targeting – from metazoans to plants to protists – Prof. William Clemons, Caltech

March 10, 2021 @ 4:00 pm – 5:00 pm
Anne Jacobs

Membrane embedded proteins are central to life bridging across bilayers from the earliest development of biological membranes. Targeting and insertion of these protein to their respective membranes is a complicated and essential process. Tail-anchor (TA) membrane proteins, found in nearly all biological membranes, are an important and diverse class that are unable to be targeted co-translationally. For eukaryotes, the GET pathway is responsible for delivering the most hydrophobic TA-clients to the endoplasmic reticulum. Our lab has focused on structural and mechanistic studies of proteins in this pathway. The pathway begins when cytoplasmic chaperones deliver the TA-client to Sgt2, which then routes the proteins to the Get3 chaperone via a Get4/Get5 hetero-tetramer. Get3 forms a stable complex with the TA-client and delivers the proteins to the ER membrane. We have characterized these complexes using structural biology and biochemistry. I will discuss an overview of the pathway from our structural perspective focused on our yeast and mammalian pathways and including our recent insights into the pathway differences in protists. From there, I will show how Get3 homologs occurred early in evolution in both archaea and bacteria. For the latter, I will provide new evidence that a cyanobacterial homolog has been conserved across evolution to occur in the chloroplasts of higher plants.

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