The structure of Get4 reveals an α-solenoid fold adapted for multiple interactions in tail-anchored protein biogenesis

Abstract 

Tail-anchored proteins play important roles in protein translocation, membrane fusion and apoptosis. They are targeted to the endoplasmic reticulum membrane via the guided-entry of tail-anchored proteins (Get) pathway. We present the 2Å crystal structure of Get4 which participates in early steps of the Get pathway. The structure shows an α-solenoid fold with particular deviations from the regular pairwise arrangement of α-helices. A conserved hydrophobic groove accommodates the flexible C-terminal region in trans. The structural organization of the Get4 helical hairpin motifs provides a scaffold for protein–protein interactions in the Get pathway.

Keywords: Get pathway, Posttranslational targeting, Tail-anchored membrane protein insertion, TPR-like fold