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-Structure paper
Title | The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase. |
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Journal, issue, pages | Science, Vol. 369, Issue 6511, Year 2020 |
Publish date | Sep 25, 2020 |
Authors | Michael J McKenna / Sue Im Sim / Alban Ordureau / Lianjie Wei / J Wade Harper / Sichen Shao / Eunyong Park / |
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- ...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. |
External links | Science / PubMed:32973005 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.3 - 3.7 Å |
Structure data | EMDB-22260, PDB-6xmp: EMDB-22261, PDB-6xmq: EMDB-22262, PDB-6xms: EMDB-22263, PDB-6xmt: EMDB-22264, PDB-6xmu: |
Chemicals | ChemComp-LMT: ChemComp-ACP: ChemComp-MG: ChemComp-ALF: ChemComp-BEF: |
Source |
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Keywords | TRANSPORT PROTEIN / P-type ATPase / transmembrane helix dislocase / protein quality control / endoplasmic reticulum |