| Online-Ressource |
Verfasst von: | Yücel, Sara Suna [VerfasserIn]  |
| Lorenzoni, Alessandra [VerfasserIn]  |
| Lemberg, Marius [VerfasserIn]  |
Titel: | The Metastable XBP1u transmembrane domain defines determinants for intramembrane proteolysis by signal peptide peptidase |
Verf.angabe: | Sara Suna Yücel, Walter Stelzer, Alessandra Lorenzoni, Manfred Wozny, Dieter Langosch, and Marius K. Lemberg |
E-Jahr: | 2019 |
Jahr: | March 12, 2019 |
Umfang: | 25 S. |
Fussnoten: | Gesehen am 24.04.2019 |
Titel Quelle: | Enthalten in: Cell reports |
Ort Quelle: | Maryland Heights, MO : Cell Press, 2012 |
Jahr Quelle: | 2019 |
Band/Heft Quelle: | 26(2019), 11, Seite 3087-3099, e1-e11 |
ISSN Quelle: | 2211-1247 |
Abstract: | Summary - Unspliced XBP1 mRNA encodes XBP1u, the transcriptionally inert variant of the unfolded protein response (UPR) transcription factor XBP1s. XBP1u targets its mRNA-ribosome-nascent-chain-complex to the endoplasmic reticulum (ER) to facilitate UPR activation and prevents overactivation. Yet, its membrane association is controversial. Here, we use cell-free translocation and cellular assays to define a moderately hydrophobic stretch in XBP1u that is sufficient to mediate insertion into the ER membrane. Mutagenesis of this transmembrane (TM) region reveals residues that facilitate XBP1u turnover by an ER-associated degradation route that is dependent on signal peptide peptidase (SPP). Furthermore, the impact of these mutations on TM helix dynamics was assessed by residue-specific amide exchange kinetics, evaluated by a semi-automated algorithm. Based on our results, we suggest that SPP-catalyzed intramembrane proteolysis of TM helices is not only determined by their conformational flexibility, but also by side-chain interactions near the scissile peptide bond with the enzyme’s active site. |
DOI: | doi:10.1016/j.celrep.2019.02.057 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1016/j.celrep.2019.02.057 |
| Volltext: http://www.sciencedirect.com/science/article/pii/S2211124719302360 |
| DOI: https://doi.org/10.1016/j.celrep.2019.02.057 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | ERAD |
| exosite |
| GxGD aspartic intramembrane protease |
| HO1 |
| regulated intramembrane proteolysis |
| SPP |
| subsite |
| transmembrane helix dynamics |
| XBP1u |
K10plus-PPN: | 1663523169 |
Verknüpfungen: | → Zeitschrift |
¬The¬ Metastable XBP1u transmembrane domain defines determinants for intramembrane proteolysis by signal peptide peptidase / Yücel, Sara Suna [VerfasserIn]; March 12, 2019 (Online-Ressource)