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Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion

Škerlová, Jana ; Berndtsson, Jens ; Nolte, Hendrik ; Ott, Martin and Stenmark, Pål LU orcid (2021) In Nature Communications 12(1).
Abstract

The pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle by converting pyruvate into acetyl-coenzyme A. PDHc encompasses three enzymatically active subunits, namely pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase. Dihydrolipoyl transacetylase is a multidomain protein comprising a varying number of lipoyl domains, a peripheral subunit-binding domain, and a catalytic domain. It forms the structural core of the complex, provides binding sites for the other enzymes, and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The molecular mechanism by which this shuttling occurs has remained elusive. Here, we report a cryo-EM... (More)

The pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle by converting pyruvate into acetyl-coenzyme A. PDHc encompasses three enzymatically active subunits, namely pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase. Dihydrolipoyl transacetylase is a multidomain protein comprising a varying number of lipoyl domains, a peripheral subunit-binding domain, and a catalytic domain. It forms the structural core of the complex, provides binding sites for the other enzymes, and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The molecular mechanism by which this shuttling occurs has remained elusive. Here, we report a cryo-EM reconstruction of the native E. coli dihydrolipoyl transacetylase core in a resting state. This structure provides molecular details of the assembly of the core and reveals how the lipoyl domains interact with the core at the active site.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
article number
5277
publisher
Nature Publishing Group
external identifiers
  • scopus:85114632548
  • pmid:34489474
ISSN
2041-1723
DOI
10.1038/s41467-021-25570-y
language
English
LU publication?
yes
id
9a17bc2b-734f-4b13-b171-5c5d1b9bdbc0
date added to LUP
2021-09-12 19:54:12
date last changed
2023-03-24 21:57:19
@article{9a17bc2b-734f-4b13-b171-5c5d1b9bdbc0,
  abstract     = {{<p>The pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle by converting pyruvate into acetyl-coenzyme A. PDHc encompasses three enzymatically active subunits, namely pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase. Dihydrolipoyl transacetylase is a multidomain protein comprising a varying number of lipoyl domains, a peripheral subunit-binding domain, and a catalytic domain. It forms the structural core of the complex, provides binding sites for the other enzymes, and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The molecular mechanism by which this shuttling occurs has remained elusive. Here, we report a cryo-EM reconstruction of the native E. coli dihydrolipoyl transacetylase core in a resting state. This structure provides molecular details of the assembly of the core and reveals how the lipoyl domains interact with the core at the active site.</p>}},
  author       = {{Škerlová, Jana and Berndtsson, Jens and Nolte, Hendrik and Ott, Martin and Stenmark, Pål}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-25570-y}},
  doi          = {{10.1038/s41467-021-25570-y}},
  volume       = {{12}},
  year         = {{2021}},
}