8d9x

Cryo-EM structure of human DELE1 in oligomeric formCryo-EM structure of human DELE1 in oligomeric form

Structural highlights

8d9x is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.8Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DELE1_HUMAN Key activator of the integrated stress response (ISR) following mitochondrial stress (PubMed:32132706, PubMed:32132707). In response to mitochondrial stress, cleaved by the protease OMA1, generating the DAP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR (PubMed:32132706, PubMed:32132707). Essential for the induction of death receptor-mediated apoptosis through the regulation of caspase activation (PubMed:20563667).^[1] ^[2] ^[3] Protein kinase activator generated by protein cleavage in response to mitochondrial stress, which accumulates in the cytosol and specifically binds to and activates the protein kinase activity of EIF2AK1/HRI (PubMed:32132706, PubMed:32132707). It thereby activates the integrated stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha (EIF2S1) phosphorylation, leading to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, the master transcriptional regulator of the ISR (PubMed:32132706, PubMed:32132707).^[4] ^[5] A0A376KDN7_ECOLX Part of the ABC transporter complex MalEFGK involved in maltose/maltodextrin import. Binds maltose and higher maltodextrins.[RuleBase:RU365005]

References

↑ Harada T, Iwai A, Miyazaki T. Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction. Apoptosis. 2010 Oct;15(10):1247-55. PMID:20563667 doi:10.1007/s10495-010-0519-3
↑ Fessler E, Eckl EM, Schmitt S, Mancilla IA, Meyer-Bender MF, Hanf M, Philippou-Massier J, Krebs S, Zischka H, Jae LT. A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol. Nature. 2020 Mar;579(7799):433-437. PMID:32132706 doi:10.1038/s41586-020-2076-4
↑ Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature. 2020 Mar;579(7799):427-432. PMID:32132707 doi:10.1038/s41586-020-2078-2
↑ Fessler E, Eckl EM, Schmitt S, Mancilla IA, Meyer-Bender MF, Hanf M, Philippou-Massier J, Krebs S, Zischka H, Jae LT. A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol. Nature. 2020 Mar;579(7799):433-437. PMID:32132706 doi:10.1038/s41586-020-2076-4
↑ Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature. 2020 Mar;579(7799):427-432. PMID:32132707 doi:10.1038/s41586-020-2078-2

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OCA

[1] Harada T, Iwai A, Miyazaki T. Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction. Apoptosis. 2010 Oct;15(10):1247-55. PMID:20563667 doi:10.1007/s10495-010-0519-3

[2] Fessler E, Eckl EM, Schmitt S, Mancilla IA, Meyer-Bender MF, Hanf M, Philippou-Massier J, Krebs S, Zischka H, Jae LT. A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol. Nature. 2020 Mar;579(7799):433-437. PMID:32132706 doi:10.1038/s41586-020-2076-4

[3] Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature. 2020 Mar;579(7799):427-432. PMID:32132707 doi:10.1038/s41586-020-2078-2

[4] Fessler E, Eckl EM, Schmitt S, Mancilla IA, Meyer-Bender MF, Hanf M, Philippou-Massier J, Krebs S, Zischka H, Jae LT. A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol. Nature. 2020 Mar;579(7799):433-437. PMID:32132706 doi:10.1038/s41586-020-2076-4

[5] Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature. 2020 Mar;579(7799):427-432. PMID:32132707 doi:10.1038/s41586-020-2078-2

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