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6xmu

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Structure of P5A-ATPase Spf1, endogenous substrate-bound

Structural highlights

6xmu is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPF1_YEAST Endoplasmic reticulum translocase required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum (PubMed:22918956, PubMed:32973005). Acts as a dislocase that mediates the ATP-dependent extraction of mislocalized mitochondrial transmembrane proteins from the endoplasmic reticulum membrane (PubMed:32973005). Specifically binds mitochondrial tail-anchored transmembrane proteins: has an atypically large substrate-binding pocket that recognizes and binds moderately hydrophobic transmembranes with short hydrophilic lumenal domains (PubMed:32973005).^[1] ^[2]

Publication Abstract from PubMed

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 Saccharomyces cerevisiae Spf1 revealed a large, membrane-accessible substrate-binding pocket that alternately faced the ER lumen and cytosol and an endogenous substrate resembling an alpha-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.

The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase.,McKenna MJ, Sim SI, Ordureau A, Wei L, Harper JW, Shao S, Park E Science. 2020 Sep 25;369(6511). pii: 369/6511/eabc5809. doi:, 10.1126/science.abc5809. PMID:32973005^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Krumpe K, Frumkin I, Herzig Y, Rimon N, Özbalci C, Brügger B, Rapaport D, Schuldiner M. Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes. Mol Biol Cell. 2012 Oct;23(20):3927-35. PMID:22918956 doi:10.1091/mbc.E11-12-0994
↑ McKenna MJ, Sim SI, Ordureau A, Wei L, Harper JW, Shao S, Park E. The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase. Science. 2020 Sep 25;369(6511). pii: 369/6511/eabc5809. doi:, 10.1126/science.abc5809. PMID:32973005 doi:http://dx.doi.org/10.1126/science.abc5809
↑ McKenna MJ, Sim SI, Ordureau A, Wei L, Harper JW, Shao S, Park E. The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase. Science. 2020 Sep 25;369(6511). pii: 369/6511/eabc5809. doi:, 10.1126/science.abc5809. PMID:32973005 doi:http://dx.doi.org/10.1126/science.abc5809