Structural highlights
Function
[ODP2_NEUCR] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3).
Publication Abstract from PubMed
The pyruvate dehydrogenase complex (PDC) is a multienzyme complex central to aerobic respiration, connecting glycolysis to mitochondrial oxidation of pyruvate. Similar to the E3-binding protein (E3BP) of mammalian PDC, PX selectively recruits E3 to the fungal PDC, but its divergent sequence suggests a distinct structural mechanism. Here, we report reconstructions of PDC from the filamentous fungus Neurospora crassa by cryo-electron microscopy, where we find protein X (PX) interior to the PDC core as opposed to substituting E2 core subunits as in mammals. Steric occlusion limits PX binding, resulting in predominantly tetrahedral symmetry, explaining previous observations in Saccharomyces cerevisiae. The PX-binding site is conserved in (and specific to) fungi, and complements possible C-terminal binding motifs in PX that are absent in mammalian E3BP. Consideration of multiple symmetries thus reveals a differential structural basis for E3BP-like function in fungal PDC.
Arrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex.,Forsberg BO, Aibara S, Howard RJ, Mortezaei N, Lindahl E Nat Commun. 2020 Sep 16;11(1):4667. doi: 10.1038/s41467-020-18401-z. PMID:32938938[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Forsberg BO, Aibara S, Howard RJ, Mortezaei N, Lindahl E. Arrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex. Nat Commun. 2020 Sep 16;11(1):4667. doi: 10.1038/s41467-020-18401-z. PMID:32938938 doi:http://dx.doi.org/10.1038/s41467-020-18401-z
