6pe0 Citations

Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction.

OpenAccess logo Elife 9 (2020)
Related entries: 6pdw, 6pdy

Cited: 22 times
EuropePMC logo PMID: 31999255

Abstract

The AAA protein Msp1 extracts mislocalized tail-anchored membrane proteins and targets them for degradation, thus maintaining proper cell organization. How Msp1 selects its substrates and firmly engages them during the energetically unfavorable extraction process remains a mystery. To address this question, we solved cryo-EM structures of Msp1-substrate complexes at near-atomic resolution. Akin to other AAA proteins, Msp1 forms hexameric spirals that translocate substrates through a central pore. A singular hydrophobic substrate recruitment site is exposed at the spiral's seam, which we propose positions the substrate for entry into the pore. There, a tight web of aromatic amino acids grips the substrate in a sequence-promiscuous, hydrophobic milieu. Elements at the intersubunit interfaces coordinate ATP hydrolysis with the subunits' positions in the spiral. We present a comprehensive model of Msp1's mechanism, which follows general architectural principles established for other AAA proteins yet specializes Msp1 for its unique role in membrane protein extraction.

Articles - 6pe0 mentioned but not cited (3)

  1. Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction. Wang L, Myasnikov A, Pan X, Walter P. Elife 9 e54031 (2020)
  2. Active conformation of the p97-p47 unfoldase complex. Xu Y, Han H, Cooney I, Guo Y, Moran NG, Zuniga NR, Price JC, Hill CP, Shen PS. Nat Commun 13 2640 (2022)
  3. Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication. Cho C, Ganser C, Uchihashi T, Kato K, Song JJ. Commun Biol 6 993 (2023)


Reviews citing this publication (6)

  1. Quality control of the mitochondrial proteome. Song J, Herrmann JM, Becker T. Nat Rev Mol Cell Biol 22 54-70 (2021)
  2. Sensing, signaling and surviving mitochondrial stress. Eckl EM, Ziegemann O, Krumwiede L, Fessler E, Jae LT. Cell Mol Life Sci 78 5925-5951 (2021)
  3. Capture and delivery of tail-anchored proteins to the endoplasmic reticulum. Farkas Á, Bohnsack KE. J Cell Biol 220 e202105004 (2021)
  4. Fidelity of Cotranslational Protein Targeting to the Endoplasmic Reticulum. Hsieh HH, Shan SO. Int J Mol Sci 23 281 (2021)
  5. Protein Quality Control at the Mitochondrial Surface. den Brave F, Gupta A, Becker T. Front Cell Dev Biol 9 795685 (2021)
  6. Looking for a safe haven: tail-anchored proteins and their membrane insertion pathways. Mehlhorn DG, Asseck LY, Grefen C. Plant Physiol 187 1916-1928 (2021)

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