期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2112107118
关键词
Actinobacteria; central metabolism; macromolecular complexes; pyruvate dehydrogenase; integrative structural biology
资金
- Agence Nationale de la Recherche (ANR) [ANR-13-JSV8-0003, ANR-18-CE92-0003]
- Institut Pasteur
- CNRS
- French Government's Investissements d'Avenir program (EQUIPEX CACSICE-Centre d'analyse de systemes complexes dans les environnements complexes) [ANR-11-EQPX-0008]
- Wuhan Institute of Biological Products Co. Ltd. (Wuhan, People's Republic of China)
- China Scholarship Council
- Agence Nationale de la Recherche (ANR) [ANR-18-CE92-0003, ANR-13-JSV8-0003] Funding Source: Agence Nationale de la Recherche (ANR)
This study reveals a unique structure of alpha-oxoacid dehydrogenase complexes in Actinobacteria, defying the traditional high-molecular weight core structure. This feature, possibly reflecting the association of PDH and ODH into a single physical complex, paves the way for therapeutic and metabolic engineering applications concerning the central nodes of pyruvate and 2-oxoglutarate in central metabolism.
alpha-oxoacid dehydrogenase complexes are large, tripartite enzymatic machineries carrying out key reactions in central metabolism. Extremely conserved across the tree of life, they have been, so far, all considered to be structured around a high-molecular weight hollow core, consisting of up to 60 subunits of the acyltransferase component. We provide here evidence that Actinobacteria break the rule by possessing an acetyltranferase component reduced to its minimally active, trimeric unit, characterized by a unique C-terminal helix bearing an actinobacterial specific insertion that precludes larger protein oligomerization. This particular feature, together with the presence of an odhA gene coding for both the decarboxylase and the acyltransferase domains on the same polypetide, is spread over Actinobacteria and reflects the association of PDH and ODH into a single physical complex. Considering the central role of the pyruvate and 2-oxoglutarate nodes in central metabolism, our findings pave the way to both therapeutic and metabolic engineering applications.
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