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-Structure paper
タイトル | DELE1 oligomerization promotes integrated stress response activation. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 30, Issue 9, Page 1295-1302, Year 2023 |
掲載日 | 2023年8月7日 |
![]() | Jie Yang / Kelsey R Baron / Daniel E Pride / Anette Schneemann / Xiaoyan Guo / Wenqian Chen / Albert S Song / Giovanni Aviles / Martin Kampmann / R Luke Wiseman / Gabriel C Lander / ![]() |
PubMed 要旨 | Mitochondria are dynamic organelles that continually respond to cellular stress. Recent studies have demonstrated that mitochondrial stress is relayed from mitochondria to the cytosol by the release ...Mitochondria are dynamic organelles that continually respond to cellular stress. Recent studies have demonstrated that mitochondrial stress is relayed from mitochondria to the cytosol by the release of a proteolytic fragment of DELE1 that binds to the eIF2α kinase HRI to initiate integrated stress response (ISR) signaling. We report the cryo-electron microscopy structure of the C-terminal cleavage product of human DELE1, which assembles into a high-order oligomer. The oligomer consists of eight DELE1 monomers that assemble with D symmetry via two sets of hydrophobic inter-subunit interactions. We identified the key residues involved in DELE1 oligomerization, and confirmed their role in stabilizing the octamer in vitro and in cells using mutagenesis. We further show that assembly-impaired DELE1 mutants are compromised in their ability to induce HRI-dependent ISR activation in cell culture models. Together, our findings provide molecular insights into the activity of DELE1 and how it signals to promote ISR activity following mitochondrial insult. |
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手法 | EM (単粒子) |
解像度 | 3.8 Å |
構造データ | EMDB-27269, PDB-8d9x: |
由来 |
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![]() | PROTEIN BINDING / Oligomer / Mitochondria / Integrated Stress Response / Kinase / Tetratricopeptide repeat |