MRPS36 provides a structural link in the eukaryotic 2-oxoglutarate dehydrogenase complex.

Hevler, Johannes F ORCID: 0000-0001-6636-7145, Albanese, Pascal ORCID: 0000-0002-0940-8534, Cabrera-Orefice, Alfredo ORCID: 0000-0002-2042-3794, Potter, Alisa ORCID: 0000-0002-5803-5340, Jankevics, Andris ORCID: 0000-0003-2095-6846, Misic, Jelena ORCID: 0000-0002-1562-0582, Scheltema, Richard A ORCID: 0000-0002-1668-0253, Brandt, Ulrich ORCID: 0000-0003-1869-6811, Arnold, Susanne ORCID: 0000-0003-2667-5156 and Heck, Albert JR ORCID: 0000-0002-2405-4404 (2023) MRPS36 provides a structural link in the eukaryotic 2-oxoglutarate dehydrogenase complex. Open biology, 13 (3). 220363-.

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Official URL: http://dx.doi.org/10.1098/rsob.220363

Abstract

The tricarboxylic acid cycle is the central pathway of energy production in eukaryotic cells and plays a key part in aerobic respiration throughout all kingdoms of life. One of the pivotal enzymes in this cycle is 2-oxoglutarate dehydrogenase complex (OGDHC), which generates NADH by oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. OGDHC is a megadalton protein complex originally thought to be assembled from three catalytically active subunits (E1o, E2o, E3). In fungi and animals, however, the protein MRPS36 has more recently been proposed as a putative additional component. Based on extensive cross-linking mass spectrometry data supported by phylogenetic analyses, we provide evidence that MRPS36 is an important member of the eukaryotic OGDHC, with no prokaryotic orthologues. Comparative sequence analysis and computational structure predictions reveal that, in contrast with bacteria and archaea, eukaryotic E2o does not contain the peripheral subunit-binding domain (PSBD), for which we propose that MRPS36 evolved as an E3 adaptor protein, functionally replacing the PSBD. We further provide a refined structural model of the complete eukaryotic OGDHC of approximately 3.45 MDa with novel mechanistic insights.

Item Type:	Article
Uncontrolled Keywords:	Eukaryotic Cells, Animals, Ketoglutarate Dehydrogenase Complex, Adaptor Proteins, Signal Transducing, Ribosomal Proteins, Phylogeny, Eukaryota
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	26 Mar 2024 11:13
Last Modified:	26 Mar 2024 15:30
DOI:	10.1098/rsob.220363
Open Access URL:	https://doi.org/10.1098/rsob.220363
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179977