The structure and function of P5A-ATPases.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Cryoelectron Microscopy* ; Endoplasmic Reticulum*/metabolism ; Adenosine Triphosphatases*/metabolism ; Adenosine Triphosphatases*/chemistry ; Adenosine Triphosphatases*/genetics; Models, Molecular ; Chaetomium/metabolism ; Chaetomium/genetics ; Chaetomium/enzymology ; Protein Domains ; Adenosine Triphosphate/metabolism
    • Abstract:
      Endoplasmic reticulum (ER) membrane resident P5A-ATPases broadly affect protein biogenesis and quality control, and yet their molecular function remains debated. Here, we report cryo-EM structures of a P5A-ATPase, CtSpf1, covering multiple transport intermediates of the E1 → E1-ATP → E1P-ADP → E1P → E2P → E2.P i  → E2 → E1 cycle. In the E2P and E2.P i states a cleft spans the entire membrane, holding a polypeptide cargo molecule. The cargo includes an ER luminal extension, pinpointed as the C-terminus in the E2.P i state, which reenters the membrane in E2P. The E1 structure harbors a cytosol-facing cavity that is blocked by an insertion we refer to as the Plug-domain. The Plug-domain is nestled to key ATPase features and is displaced in the E1P-ADP and E1P states. Collectively, our findings are compatible with a broad range of proteins as cargo, with the P5A-ATPases serving a role in membrane removal of helices, although insertion/secretion cannot be excluded, as well as with a mechanistic role of the Plug-domain.
      (© 2024. The Author(s).)
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    • Grant Information:
      2015.0131 Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation); 2020.0194 Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation); R313-2019-774 Lundbeckfonden (Lundbeck Foundation); R346-2020-2019 Lundbeckfonden (Lundbeck Foundation); R322-2019-2588 Lundbeckfonden (Lundbeck Foundation); R324-2019-1855 Lundbeckfonden (Lundbeck Foundation); 21:1773 Carl Tryggers Stiftelse för Vetenskaplig Forskning (Carl Trygger Foundation); 20200739 Crafoordska Stiftelsen (Crafoord Foundation); 20220905 Crafoordska Stiftelsen (Crafoord Foundation); n/a Kungliga Fysiografiska Sällskapet i Lund (Royal Physiographic Society in Lund)
    • Accession Number:
      EC 3.6.1.- (Adenosine Triphosphatases)
      8L70Q75FXE (Adenosine Triphosphate)
    • Subject Terms:
      Chaetomium thermophilum
    • Publication Date:
      Date Created: 20241106 Date Completed: 20241106 Latest Revision: 20241109
    • Publication Date:
      20241109
    • Accession Number:
      PMC11541931
    • Accession Number:
      10.1038/s41467-024-53757-6
    • Accession Number:
      39505844