Walter Lab

  • Walter Lab
  • Research
    • The Unfolded Protein Response and IRE1 Signaling in Health and Disease
    • Organellar quality control, dynamics, and inheritance
    • RNA processing in the unfolded protein response
    • The integrated stress response and its role in cognition
    • ATF6-branch signaling through regulated proteolysis
  • Lab Members
    • Current
    • Alumni
  • Contact Us
  • Social
  • Publications
  • News & Notes

Conserved structural elements specialize ATAD1 as a membrane protein extraction machine

Wang L, Toutkoushian H, Belyy V, Kokontis C, Walter P. Conserved structural elements specialize ATAD1 as a membrane protein extraction machine. bioRxiv DOI: 10.1101/2021.09.24.461712, 2021
( PMID : not available ) (PDF)

Abstract

The mitochondrial AAA protein ATAD1 (in humans; Msp1 in yeast) removes mislocalized membrane proteins, as well as stuck import substrates from the mitochondrial outer membrane, facilitating their re-insertion into their cognate organelles and maintaining mitochondria’s protein import capacity. In doing so, it helps to maintain proteostasis in mitochondria. How ATAD1 tackles the energetic challenge to extract hydrophobic membrane proteins from the lipid bilayer and what structural features adapt ATAD1 for its particular function has remained a mystery. Previously, we determined the structure of Msp1 in complex with a peptide substrate (Wang et al., 2020). The structure showed that Msp1’s mechanism follows the general principle established for AAA proteins while adopting several structural features that specialize it for its function. We used the yeast growth assay to test the function of key amino acids within these structural elements. In this work, we determined the cryo-EM structures of the human ATAD1 in complex with a peptide substrate at near atomic resolution. The structures show that phylogenetically conserved structural elements adapt ATAD1 for its function while generally adopting a conserved mechanism shared by many AAA proteins. ATAD1’s distinguishing features include an abundance of aromatic amino acids that line the central pore proposed to give ATAD1 a firm grip on its substrate and a short a-helix at the C-terminus that strongly facilitates ATAD1’s oligomerization. We also developed a microscopy-based assay reporting on protein mislocalization, with which we directly assessed ATAD1’s activity in live cells.


Deprecated: genesis_footer_creds_text is deprecated since version 3.1.0! Use genesis_pre_get_option_footer_text instead. This filter is no longer supported. You can now modify your footer text using the Theme Settings. in /nas/content/live/wlabdemo/wp-includes/functions.php on line 5698

Copyright © 2022  Walter Lab | University of California, San Francisco | Howard Hughes Medical Institute