Aichem, Annette and Anders, Samira and Catone, Nicola and Roessler, Philip and Stotz, Sophie and Berg, Andrej and Schwab, Ricarda and Scheuermann, Sophia and Bialas, Johanna and Schuetz-Stoffregen, Mira C. and Schmidtke, Gunter and Peter, Christine and Groettrup, Marcus and Wiesner, Silke (2018) The structure of the ubiquitin-like modifier FAT10 reveals an alternative targeting mechanism for proteasomal degradation. NATURE COMMUNICATIONS, 9: 3321. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MULTIPLE SEQUENCE ALIGNMENT; 26S PROTEASOME; PROTEIN FAT10; PROTEOMIC ANALYSIS; MAMMALIAN-CELLS; AAA-ATPASE; SYSTEM; CANCER; FIELD; MACROMOLECULES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Jan 2020 09:46 |
| Last Modified: | 10 Jan 2020 09:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14035 |
Actions (login required)
 |
View Item |
