7OTT

Metabolon-embedded pyruvate dehydrogenase complex E2 core at near-atomic resolution

7OTT の概要

• エントリーDOI: 10.2210/pdb7ott/pdb
• EMDBエントリー: 13066
• 分子名称: Acetyltransferase component of pyruvate dehydrogenase complex (1 entity in total)
• 機能のキーワード: pyruvate, dehydrogenase, complex, e2, core, c.thermophilum, metabolon, transferase
• 由来する生物種: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48777.49

構造登録者

Tueting, C.,Kastritis, P.L. (登録日: 2021-06-10, 公開日: 2021-12-01, 最終更新日: 2024-07-17)

主引用文献

Tuting, C.,Kyrilis, F.L.,Muller, J.,Sorokina, M.,Skalidis, I.,Hamdi, F.,Sadian, Y.,Kastritis, P.L.
Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction.
Nat Commun, 12:6933-6933, 2021

PubMed Abstract: Found across all kingdoms of life, 2-keto acid dehydrogenase complexes possess prominent metabolic roles and form major regulatory sites. Although their component structures are known, their higher-order organization is highly heterogeneous, not only across species or tissues but also even within a single cell. Here, we report a cryo-EM structure of the fully active Chaetomium thermophilum pyruvate dehydrogenase complex (PDHc) core scaffold at 3.85 Å resolution (FSC = 0.143) from native cell extracts. By combining cryo-EM with macromolecular docking and molecular dynamics simulations, we resolve all PDHc core scaffold interfaces and dissect the residing transacetylase reaction. Electrostatics attract the lipoyl domain to the transacetylase active site and stabilize the coenzyme A, while apolar interactions position the lipoate in its binding cleft. Our results have direct implications on the structural determinants of the transacetylase reaction and the role of flexible regions in the context of the overall 10 MDa PDHc metabolon architecture.

PubMed: 34836937
DOI: 10.1038/s41467-021-27287-4

実験手法

ELECTRON MICROSCOPY (3.84 Å)