Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex

Jiansen Jiang, Flavius L. Baiesc, Yasuaki Hiromasa, Xuekui Yu, Wong Hoi Hui, Xinghong Dai, Thomas E. Roche, Z. Hong Zhou

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Abstract

Pyruvate dehydrogenase complex (PDC) is a large multienzyme complex that catalyzes the irreversible conversion of pyruvate to acetyl-coenzyme A with reduction of NAD+. Distinctive from PDCs in lower forms of life, in mammalian PDC, dihydrolipoyl acetyltransferase (E2; E2p in PDC) and dihydrolipoamide dehydrogenase binding protein (E3BP) combine to form a complex that plays a central role in the organization, regulation, and integration of catalytic reactions of PDC. However, the atomic structure and organization of the mammalian E2p/E3BP heterocomplex are unknown. Here, we report the structure of the recombinant dodecahedral core formed by the C-terminal inner-core/catalytic (IC) domain of human E2p determined at 3.1 Å resolution by cryo electron microscopy (cryoEM). The structure of the N-terminal fragment and four other surface areas of the human E2p IC domain exhibit significant differences from those of the other E2 crystal structures, which may have implications for the integration of E3BP in mammals. This structure also allowed us to obtain a homology model for the highly homologous IC domain of E3BP. Analysis of the interactions of human E2p or E3BP with their adjacent IC domains in the dodecahedron provides new insights into the organization of the E2p/E3BP heterocomplex and suggests a potential contribution by E3BP to catalysis in mammalian PDC.

Original languageEnglish
Pages (from-to)2325-2334
Number of pages10
JournalBiochemistry
Volume57
Issue number16
DOIs
Publication statusPublished - Apr 24 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Jiang, J., Baiesc, F. L., Hiromasa, Y., Yu, X., Hui, W. H., Dai, X., Roche, T. E., & Zhou, Z. H. (2018). Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex. Biochemistry, 57(16), 2325-2334. https://doi.org/10.1021/acs.biochem.8b00357