Get4/5-mediated remodeling of Get3's substrate-binding chamber: Insights into tail-anchored protein targeting by the GET pathway.

ABSTRACT: The Guided Entry of Tail-Anchored Proteins (GET) pathway ensures accurate targeting of Tail-Anchored proteins (TAs)-a diverse class of membrane proteins-to the endoplasmic reticulum (ER) membrane. In yeast, newly synthesized TAs are captured by Sgt2 and transferred to Get3 for delivery to the ER, where they undergo subsequent membrane insertion. Efficient and protected handoff of hydrophobic TAs from Sgt2 to Get3 is facilitated by the Get4/5 complex, which is thought to act as a scaffold to position TA-bound Sgt2 and Get3 in proximity while trapping Get3 in an ATP-bound conformation necessary for TA binding. To define the molecular basis for this process, we determined the cryo-EM structure of the Saccharomyces cerevisiae Get3-Get4/5 complex at 3.2 Å resolution. Our structure shows that Ge

SUBMITTER: Granados-Villanueva D 

PROVIDER: S-EPMC12506534 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature