9Y72

Structure of Mycobacterium tuberculosis pyruvate dehydrogenase complex E2p core subunit DlaT in a two-hexamer state

これはPDB形式変換不可エントリーです。

9Y72 の概要

• エントリーDOI: 10.2210/pdb9y72/pdb
• EMDBエントリー: 72630 72639
• 分子名称: Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (1 entity in total)
• 機能のキーワード: two-hexamer dihydrolipoamide acetyltransferase mycobacterium tuberculosis pyruvate dehydrogenase complex, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 311416.94

構造登録者

Hsu, H.C.,Li, H. (登録日: 2025-09-09, 公開日: 2026-02-25, 最終更新日: 2026-03-25)

主引用文献

Hsu, H.C.,Bonnet, I.,Bryk, R.,Li, H.
Mycobacterium tuberculosis assembles a unique hexameric E2p core of the pyruvate dehydrogenase complex.
J.Biol.Chem., 302:111284-111284, 2026

PubMed Abstract: The pyruvate dehydrogenase complex (PDHc) is a universally conserved multienzyme system that converts pyruvate into acetyl-CoA for entry into the TCA cycle and for NADH production. Its central scaffold, the dihydrolipoyl transacetylase (E2p), forms an oligomeric inner core that recruits pyruvate dehydrogenase (E1p) and dihydrolipoyl dehydrogenase (E3). All previously characterized PDHc assemblies adopt either an octahedral 24-mer or an icosahedral 60-mer E2p core, each constructed from trimeric building blocks. We recently showed that the Mycobacterium tuberculosis (Mtb) E2p protein DlaT also functions as the core of the pathogen's peroxynitrite reductase/peroxidase (PNR/P) complex. Here, using cryo-EM, we demonstrate that DlaT assembles into discrete hexamers and dodecamers at micromolar concentrations, which approximate intracellular DlaT concentrations in Mtb. Structure-guided mutagenesis combined with in vitro activity assays indicate that the hexamer represents the functional E2p core of the Mtb PDHc. This noncanonical architecture arises from unique interfaces between DlaT trimers that preclude formation of the classic spherical 24- or 60-mer structures. We propose that this specialized E2p organization enables Mtb to regulate metabolic activities and to remodel the E2p core for engagement in the PNR/P antioxidant pathway under stress. Our findings reveal an unexpected diversity in PDHc architecture and uncover a distinct organization principle for the core metabolic complex in mycobacteria.

PubMed: 41690596
DOI: 10.1016/j.jbc.2026.111284

実験手法

ELECTRON MICROSCOPY (2.51 Å)