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Hydrophobic handoff for direct delivery of peroxisome tail-anchored proteins

Author

Listed:
  • Yinxiao Chen

    (Temasek Life Sciences Laboratory, National University of Singapore)

  • Laurent Pieuchot

    (Temasek Life Sciences Laboratory, National University of Singapore)

  • Rachel Ann Loh

    (Temasek Life Sciences Laboratory, National University of Singapore)

  • Jing Yang

    (Temasek Life Sciences Laboratory, National University of Singapore)

  • Teuku Mahfuzh Aufar Kari

    (Temasek Life Sciences Laboratory, National University of Singapore)

  • Jie Yun Wong

    (Temasek Life Sciences Laboratory, National University of Singapore)

  • Gregory Jedd

    (Temasek Life Sciences Laboratory, National University of Singapore)

Abstract

Tail-anchored (TA) proteins are inserted into membranes post-translationally through a C-terminal transmembrane domain (TMD). The PEX19 protein binds peroxisome TA proteins in the cytoplasm and delivers them to the membrane through the PEX3 receptor protein. An amphipathic segment in PEX19 promotes docking on PEX3. However, how this leads to substrate insertion is unknown. Here we reconstitute peroxisome TA protein biogenesis into two sequential steps of substrate TMD engagement and membrane insertion. We identify a series of previously uncharacterized amphipathic segments in PEX19 and identify one whose hydrophobicity is required for membrane insertion, but not TMD chaperone activity or PEX3 binding. A membrane-proximal hydrophobic surface of PEX3 promotes an unconventional form of membrane intercalation, and is also required for TMD insertion. Together, these data support a mechanism in which hydrophobic moieties in the TMD chaperone and its membrane-associated receptor act in a concerted manner to prompt TMD release and membrane insertion.

Suggested Citation

  • Yinxiao Chen & Laurent Pieuchot & Rachel Ann Loh & Jing Yang & Teuku Mahfuzh Aufar Kari & Jie Yun Wong & Gregory Jedd, 2014. "Hydrophobic handoff for direct delivery of peroxisome tail-anchored proteins," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6790
    DOI: 10.1038/ncomms6790
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    Cited by:

    1. Jeonghyun Oh & Christy Catherine & Eun Seon Kim & Kwang Wook Min & Hae Chan Jeong & Hyojin Kim & Mijin Kim & Seung Hae Ahn & Nataliia Lukianenko & Min Gu Jo & Hyeon Seok Bak & Sungsu Lim & Yun Kyung K, 2025. "Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin," Nature Communications, Nature, vol. 16(1), pages 1-17, December.

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