Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase
العنوان: | Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase |
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المؤلفون: | Yue Dai, Angela S. Fleischhacker, Liu Liu, Sara Fayad, Amanda L. Gunawan, Dennis J. Stuehr, Stephen W. Ragsdale |
المصدر: | Biol Chem |
بيانات النشر: | Walter de Gruyter GmbH, 2022. |
سنة النشر: | 2022 |
مصطلحات موضوعية: | HEK293 Cells, Heme Oxygenase (Decyclizing), Clinical Biochemistry, Humans, Glyceraldehyde-3-Phosphate Dehydrogenases, Heme, Molecular Biology, Biochemistry, Article |
الوصف: | Heme regulatory motifs (HRMs) are found in a variety of proteins with diverse biological functions. In heme oxygenase-2 (HO2), heme binds to the HRMs and is readily transferred to the catalytic site in the core of the protein. To further define this heme transfer mechanism, we evaluated the ability of GAPDH, a known heme chaperone, to transfer heme to the HRMs and/or the catalytic core of HO2. Our results indicate GAPDH and HO2 form a complex in vitro. We have followed heme insertion at both sites by fluorescence quenching in HEK293 cells with HO2 reporter constructs. Upon mutation of residues essential for heme binding at each site in our reporter construct, we found that HO2 binds heme at the core and the HRMs in live cells and that heme delivery to HO2 is dependent on the presence of GAPDH that is competent for heme binding. In sum, GAPDH is involved in heme delivery to HO2 but, surprisingly, not to a specific site on HO2. Our results thus emphasize the importance of heme binding to both the core and the HRMs and the interplay of HO2 with the heme pool via GAPDH to maintain cellular heme homeostasis. |
تدمد: | 1437-4315 1431-6730 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e1c4358754bc082ce25f88af57ff04fTest https://doi.org/10.1515/hsz-2022-0230Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....8e1c4358754bc082ce25f88af57ff04f |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14374315 14316730 |
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