Please use this identifier to cite or link to this item:
Title: Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction
Author(s): Tüting, Christian
Kyrilis, Fotis L.
Müller, Johannes
Sorokina, Marija
Skalidis, Ioannis
Hamdi, Farzad
Sadian, Yashar
Kastritis, Panagiotis L.
Issue Date: 2021
Type: Article
Language: English
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.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Publikationsfonds MLU
Journal Title: Nature Communications
Publisher: Nature Publishing Group UK
Publisher Place: [London]
Volume: 12
Original Publication: 10.1038/s41467-021-27287-4
Appears in Collections:Open Access Publikationen der MLU

Files in This Item:
File Description SizeFormat 
s41467-021-27287-4.pdf5.13 MBAdobe PDFThumbnail