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Structure paper

タイトル	Stoichiometry and architecture of the human pyruvate dehydrogenase complex.
ジャーナル・号・ページ	Sci Adv, Vol. 10, Issue 29, Page eadn4582, Year 2024
掲載日	2024年7月19日
著者	Rafal Zdanowicz / Pavel Afanasyev / Adam Pruška / Julian A Harrison / Christoph Giese / Daniel Boehringer / Alexander Leitner / Renato Zenobi / Rudi Glockshuber /
PubMed 要旨	The pyruvate dehydrogenase complex (PDHc) is a key megaenzyme linking glycolysis with the citric acid cycle. In mammalian PDHc, dihydrolipoamide acetyltransferase (E2) and the dihydrolipoamide ...The pyruvate dehydrogenase complex (PDHc) is a key megaenzyme linking glycolysis with the citric acid cycle. In mammalian PDHc, dihydrolipoamide acetyltransferase (E2) and the dihydrolipoamide dehydrogenase-binding protein (E3BP) form a 60-subunit core that associates with the peripheral subunits pyruvate dehydrogenase (E1) and dihydrolipoamide dehydrogenase (E3). The structure and stoichiometry of the fully assembled, mammalian PDHc or its core remained elusive. Here, we demonstrate that the human PDHc core is formed by 48 E2 copies that bind 48 E1 heterotetramers and 12 E3BP copies that bind 12 E3 homodimers. Cryo-electron microscopy, together with native and cross-linking mass spectrometry, confirmed a core model in which 8 E2 homotrimers and 12 E2-E2-E3BP heterotrimers assemble into a pseudoicosahedral particle such that the 12 E3BP molecules form six E3BP-E3BP intertrimer interfaces distributed tetrahedrally within the 60-subunit core. The even distribution of E3 subunits in the peripheral shell of PDHc guarantees maximum enzymatic activity of the megaenzyme.
リンク	Sci Adv / PubMed:39018392 / PubMed Central
手法	EM (単粒子)
解像度	2.9 - 3.7 Å
構造データ	17691 8piu EMDB-17691: 60-meric complex of dihydrolipoamide acetyltransferase (E2) of the human pyruvate dehydrogenase complex (icosahedral symmetry) PDB-8piu: 60-meric complex of dihydrolipoamide acetyltransferase (E2) of the human pyruvate dehydrogenase complex 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-17694: 60-meric complex of dihydrolipoamide acetyltransferase (E2) of the human pyruvate dehydrogenase complex (tetrahedral symmetry) 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-18616: E2/E3BP core of the human pyruvate dehydrogenase complex (map 1; 3.4 A) 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-18617: E2/E3BP core of the human pyruvate dehydrogenase complex (map 2; 3.7 A) 手法: EM (単粒子) / 解像度: 3.7 Å
由来	homo sapiens (ヒト)
キーワード	TRANSFERASE / pyruvate dehydrogenase complex / PDHc / E2 / cryo-EM