6XMU

Structure of P5A-ATPase Spf1, endogenous substrate-bound

Summary for 6XMU

• Entry DOI: 10.2210/pdb6xmu/pdb
• EMDB information: 22264
• Descriptor: P5A-type ATPase, Putative endogenous substrate transmembrane helix, BERYLLIUM TRIFLUORIDE ION, ... (4 entities in total)
• Functional Keywords: p-type atpase, transmembrane helix dislocase, protein quality control, endoplasmic reticulum, transport protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 139383.58

Authors

Park, E.,Sim, S.I. (deposition date: 2020-06-30, release date: 2020-09-23, Last modification date: 2024-03-06)

Primary citation

McKenna, M.J.,Sim, S.I.,Ordureau, A.,Wei, L.,Harper, J.W.,Shao, S.,Park, E.
The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase.
Science, 369:-, 2020

PubMed Abstract: Organelle identity depends on protein composition. How mistargeted proteins are selectively recognized and removed from organelles is incompletely understood. Here, we found that the orphan P5A-adenosine triphosphatase (ATPase) transporter ATP13A1 (Spf1 in yeast) directly interacted with the transmembrane segment (TM) of mitochondrial tail-anchored proteins. P5A-ATPase activity mediated the extraction of mistargeted proteins from the endoplasmic reticulum (ER). Cryo-electron microscopy structures of Spf1 revealed a large, membrane-accessible substrate-binding pocket that alternately faced the ER lumen and cytosol and an endogenous substrate resembling an α-helical TM. Our results indicate that the P5A-ATPase could dislocate misinserted hydrophobic helices flanked by short basic segments from the ER. TM dislocation by the P5A-ATPase establishes an additional class of P-type ATPase substrates and may correct mistakes in protein targeting or topogenesis.

PubMed: 32973005
DOI: 10.1126/science.abc5809

Experimental method

ELECTRON MICROSCOPY (3.3 Å)