| Online-Ressource |
Verfasst von: | Zhang, Panpan [VerfasserIn]  |
| Maruoka, Masahiro [VerfasserIn]  |
| Suzuki, Ryo [VerfasserIn]  |
| Katani, Hikaru [VerfasserIn]  |
| Dou, Yu [VerfasserIn]  |
| Packwood, Daniel M. [VerfasserIn]  |
| Kosako, Hidetaka [VerfasserIn]  |
| Tanaka, Motomu [VerfasserIn]  |
| Suzuki, Jun [VerfasserIn]  |
Titel: | Extracellular calcium functions as a molecular glue for transmembrane helices to activate the scramblase Xkr4 |
Verf.angabe: | Panpan Zhang, Masahiro Maruoka, Ryo Suzuki, Hikaru Katani, Yu Dou, Daniel M Packwood, Hidetaka Kosako, Motomu Tanaka & Jun Suzuki |
E-Jahr: | 2023 |
Jahr: | 11 September 2023 |
Umfang: | 13 S. |
Illustrationen: | Illustrationen |
Fussnoten: | Gesehen am 06.12.2024 |
Titel Quelle: | Enthalten in: Nature Communications |
Ort Quelle: | [London] : Springer Nature, 2010 |
Jahr Quelle: | 2023 |
Band/Heft Quelle: | 14(2023), Artikel-ID 5592, Seite 1-13 |
ISSN Quelle: | 2041-1723 |
Abstract: | The "eat me" signal, phosphatidylserine is exposed on the surface of dying cells by phospholipid scrambling. Previously, we showed that the Xkr family protein Xkr4 is activated by caspase-mediated cleavage and binding of the XRCC4 fragment. Here, we show that extracellular calcium is an additional factor needed to activate Xkr4. The constitutively active mutant of Xkr4 is found to induce phospholipid scrambling in an extracellular, but not intracellular, calcium-dependent manner. Importantly, other Xkr family members also require extracellular calcium for activation. Alanine scanning shows that D123 and D127 of TM1 and E310 of TM3 coordinate calcium binding. Moreover, lysine scanning demonstrates that the E310K mutation-mediated salt bridge between TM1 and TM3 bypasses the requirement of calcium. Cysteine scanning proves that disulfide bond formation between TM1 and TM3 also activates phospholipid scrambling without calcium. Collectively, this study shows that extracellular calcium functions as a molecular glue for TM1 and TM3 of Xkr proteins for activation, thus demonstrating a regulatory mechanism for multi-transmembrane region-containing proteins. Dying cells display an "eat me" signal through phospholipid scrambling. Here, the authors show that activation of the plasma membrane-bound Xkr4 scramblase requires extracellular calcium as a "molecular glue" for connecting transmembrane regions. |
DOI: | doi:10.1038/s41467-023-40934-2 |
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.
kostenfrei: Volltext: https://doi.org/10.1038/s41467-023-40934-2 |
| kostenfrei: Volltext: https://www.nature.com/articles/s41467-023-40934-2#citeas |
| DOI: https://doi.org/10.1038/s41467-023-40934-2 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | CLEARANCE |
| COMPLEX |
| DYNAMICS |
| EXPRESSION |
| PHOSPHATIDYLSERINE EXPOSURE |
| PROTEIN |
| RECEPTOR |
K10plus-PPN: | 191113003X |
Verknüpfungen: | → Zeitschrift |
Extracellular calcium functions as a molecular glue for transmembrane helices to activate the scramblase Xkr4 / Zhang, Panpan [VerfasserIn]; 11 September 2023 (Online-Ressource)