Unité de Microbiologie Structurale, Institut Pasteur, CNRS, Université de Paris, 75015 Paris, France;
Unité de Microbiologie Structurale, Institut Pasteur, CNRS, Université de Paris, 75015 Paris, France.
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48). doi: 10.1073/pnas.2112107118.
α-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 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.
α-酮酸脱氢酶复合物是大型的三联酶机器，在中心代谢中执行关键反应。它们在生命之树上高度保守，迄今为止，人们一直认为它们的结构都围绕着一个高分子量的中空核心，由多达 60 个酰基转移酶组件的亚基组成。我们在这里提供的证据表明，放线菌打破了这一规则，其乙酰基转移酶组件减少到最小活性的三聚体单元，其特征是带有一个独特的 C 末端螺旋，带有放线菌特有的插入，阻止了更大的蛋白质寡聚化。这种特殊的特征，以及在同一多肽上同时存在编码脱羧酶和酰基转移酶结构域的 基因，在放线菌中广泛存在，反映了 PDH 和 ODH 结合成一个单一的物理复合物。考虑到丙酮酸和 2-酮戊二酸节点在中心代谢中的核心作用，我们的发现为治疗和代谢工程应用铺平了道路。
