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The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase
Michael J McKenna1, Sue Im Sim2, Alban Ordureau1
1Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|September 25, 2020
Summary
The P5A-ATPase transporter Spf1 extracts mistargeted transmembrane proteins from the endoplasmic reticulum. This discovery reveals a new mechanism for correcting protein targeting errors.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Organelle identity relies on precise protein composition.
- Mechanisms for removing mistargeted proteins from organelles are not fully understood.
Purpose of the Study:
- To investigate the role of P5A-adenosine triphosphatase (ATPase) transporter ATP13A1 (Spf1) in protein quality control.
- To elucidate how mistargeted proteins are recognized and removed from the endoplasmic reticulum (ER).
Main Methods:
- Utilized cryo-electron microscopy to determine the structure of Saccharomyces cerevisiae Spf1.
- Investigated the interaction between Spf1 and transmembrane segments of tail-anchored proteins.
- Assessed P5A-ATPase activity in protein extraction from the ER.
Main Results:
- Spf1 directly interacts with the transmembrane segments of tail-anchored proteins.
- P5A-ATPase activity facilitates the extraction of mistargeted proteins from the ER.
- Structural analysis revealed a substrate-binding pocket capable of binding alpha-helical transmembrane segments.
Conclusions:
- The P5A-ATPase can dislocate misinserted hydrophobic helices from the ER.
- This TM dislocation by P5A-ATPase represents a new class of P-type ATPase substrates.
- This mechanism may correct errors in protein targeting and topogenesis.
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