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TitleThe endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase.
Journal, issue, pagesScience, Vol. 369, Issue 6511, Year 2020
Publish dateSep 25, 2020
AuthorsMichael J McKenna / Sue Im Sim / Alban Ordureau / Lianjie Wei / J Wade Harper / Sichen Shao / Eunyong Park /
PubMed AbstractOrganelle 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 linksScience / PubMed:32973005 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.7 Å
Structure data

EMDB-22260, PDB-6xmp:
Structure of P5A-ATPase Spf1, Apo form
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-22261, PDB-6xmq:
Structure of P5A-ATPase Spf1, AMP-PCP-bound form
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-22262, PDB-6xms:
Structure of P5A-ATPase Spf1, AlF4-bound form
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-22263, PDB-6xmt:
Structure of P5A-ATPase Spf1, BeF3-bound form
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-22264, PDB-6xmu:
Structure of P5A-ATPase Spf1, endogenous substrate-bound
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

ChemComp-ACP:
PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / AMP-PCP, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

ChemComp-ALF:
TETRAFLUOROALUMINATE ION

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

Source
  • Saccharomyces cerevisiae (brewer's yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
KeywordsTRANSPORT PROTEIN / P-type ATPase / transmembrane helix dislocase / protein quality control / endoplasmic reticulum

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