The structure of the ubiquitin-like modifier FAT10 reveals an alternative targeting mechanism for proteasomal degradation

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Nature Communications. 2018, 9, 3321. eISSN 2041-1723. Available under: doi: 10.1038/s41467-018-05776-3
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FAT10 is a ubiquitin-like modifier that directly targets proteins for proteasomal degradation. Here, we report the high-resolution structures of the two individual ubiquitin-like domains (UBD) of FAT10 that are joined by a flexible linker. While the UBDs of FAT10 show the typical ubiquitin-fold, their surfaces are entirely different from each other and from ubiquitin explaining their unique binding specificities. Deletion of the linker abrogates FAT10-conjugation while its mutation blocks auto-FAT10ylation of the FAT10-conjugating enzyme USE1 but not bulk conjugate formation. FAT10- but not ubiquitin-mediated degradation is independent of the segregase VCP/p97 in the presence but not the absence of FAT10's unstructured N-terminal heptapeptide. Stabilization of the FAT10 UBDs strongly decelerates degradation suggesting that the intrinsic instability of FAT10 together with its disordered N-terminus enables the rapid, joint degradation of FAT10 and its substrates without the need for FAT10 de-conjugation and partial substrate unfolding.

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ISO 690AICHEM, Annette, Nicola CATONE, Andrej BERG, Ricarda SCHWAB, Sophia SCHEUERMANN, Johanna BIALAS, Gunter SCHMIDTKE, Christine PETER, Marcus GRÖTTRUP, Silke WIESNER, 2018. The structure of the ubiquitin-like modifier FAT10 reveals an alternative targeting mechanism for proteasomal degradation. In: Nature Communications. 2018, 9, 3321. eISSN 2041-1723. Available under: doi: 10.1038/s41467-018-05776-3
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@article{Aichem2018-08-20struc-43140,
  year={2018},
  doi={10.1038/s41467-018-05776-3},
  title={The structure of the ubiquitin-like modifier FAT10 reveals an alternative targeting mechanism for proteasomal degradation},
  volume={9},
  journal={Nature Communications},
  author={Aichem, Annette and Catone, Nicola and Berg, Andrej and Schwab, Ricarda and Scheuermann, Sophia and Bialas, Johanna and Schmidtke, Gunter and Peter, Christine and Gröttrup, Marcus and Wiesner, Silke},
  note={Author Correction zu diesem Artikel: https://doi.org/10.1038/s41467-018-07183-0 Article Number: 3321}
}
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Author Correction zu diesem Artikel: https://doi.org/10.1038/s41467-018-07183-0
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