7q5r
Protein community member pyruvate dehydrogenase complex E2 core from C. thermophilumProtein community member pyruvate dehydrogenase complex E2 core from C. thermophilum
Structural highlights
FunctionODP2_CHATD The 10-megadalton pyruvate dehydrogenase complex contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) and catalyzes the overall oxidative decarboxylation of pyruvate to form acetyl-CoA and CO(2) (PubMed:33567276, PubMed:34836937, PubMed:35093201). Within the complex, pyruvate and thiamine pyrophosphate (TPP or vitamin B1) are bound by pyruvate dehydrogenase E1 subunits alpha and beta and pyruvate is decarboxylated leading to the 2-carbon hydrohyethyl bound to TPP. The E2 component contains covalently-bound lipoyl cofactors and transfers the hydroxyethyl group from TPP to an oxidized form of covalently bound lipoamide, and the resulting acetyl group is then transferred to free coenzyme A to form acetyl-CoA and reduced dihydrolipoamide-E2. Finally, the flavoprotein dihydrolipoamide dehydrogenase (E3) re-oxidizes the lipoyl group of dihydrolipoamide-E2 to form lipoamide-E2 and NADH. A fourth subunit, E3BP, is responsible for tethering E3 in proximity to the core, forming the entire metabolon (Probable).[1] [2] [3] [4] Publication Abstract from PubMedCellular function is underlined by megadalton assemblies organizing in proximity, forming communities. Metabolons are protein communities involving metabolic pathways such as protein, fatty acid, and thioesters of coenzyme-A synthesis. Metabolons are highly heterogeneous due to their function, making their analysis particularly challenging. Here, we simultaneously characterize metabolon-embedded architectures of a 60S pre-ribosome, fatty acid synthase, and pyruvate/oxoglutarate dehydrogenase complex E2 cores de novo. Cryo-electron microscopy (cryo-EM) 3D reconstructions are resolved at 3.84-4.52 A resolution by collecting <3,000 micrographs of a single cellular fraction. After combining cryo-EM with artificial intelligence-based atomic modeling and de novo sequence identification methods, at this resolution range, polypeptide hydrogen bonding patterns are discernible. Residing molecular components resemble their purified counterparts from other eukaryotes but also exhibit substantial conformational variation with potential functional implications. Our results propose an integrated tool, boosted by machine learning, that opens doors for structural systems biology spearheaded by cryo-EM characterization of native cell extracts. Cryo-EM and artificial intelligence visualize endogenous protein community members.,Skalidis I, Kyrilis FL, Tuting C, Hamdi F, Chojnowski G, Kastritis PL Structure. 2022 Jan 19. pii: S0969-2126(22)00001-6. doi:, 10.1016/j.str.2022.01.001. PMID:35093201[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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