丙酮酸脱氢酶复合体的E2内核的原子结构。,Biochemistry

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丙酮酸脱氢酶复合体的E2内核的原子结构。
Biochemistry ( IF 2.9 ) Pub Date : 2018-04-02 00:00:00 , DOI: 10.1021/acs.biochem.8b00357
Jiansen Jiang _{1,

2} , Flavius L. Baiesc ₁ , Yasuaki Hiromasa _{3,

4} , Xuekui Yu _{1,

2} , Wong Hoi Hui ₂ , Xinghong Dai _{1,

2} , Thomas E. Roche ₄ , Z. Hong Zhou _{1,

2}

Affiliation

丙酮酸脱氢酶复合物（PDC）是一种大型的多酶复合物，可催化丙酮酸不可逆地转化为乙酰辅酶A，同时降低NAD ⁺。在哺乳动物的PDC中，与低水平的PDC不同，二氢脂酰乙酰基转移酶（E2； PDC中的E2p）和二氢脂酰胺脱氢酶结合蛋白（E3BP）结合形成复合物，该复合物在催化的组织，调控和整合中起着核心作用PDC的反应。但是，哺乳动物E2p / E3BP异源复合物的原子结构和组织是未知的。在这里，我们报告由人E2p的C末端内核/催化（IC）域形成的重组十二面体核心的结构，该结构由冷冻电子显微镜（cryoEM）确定为3.1Å分辨率。人E2p IC域的N末端片段和其他四个表面积的结构与其他E2晶体结构存在显着差异，这可能与哺乳动物中E3BP的整合有关。这种结构还使我们能够获得E3BP的高度同源IC结构域的同源性模型。人E2p或E3BP与十二面体中相邻IC域的相互作用的分析为E2p / E3BP异质复合物的组织提供了新见解，并暗示了E3BP对哺乳动物PDC催化的潜在贡献。

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Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex

Pyruvate dehydrogenase complex (PDC) is a large multienzyme complex that catalyzes the irreversible conversion of pyruvate to acetyl-coenzyme A with reduction of NAD⁺. Distinctive from PDCs in lower forms of life, in mammalian PDC, dihydrolipoyl acetyltransferase (E2; E2p in PDC) and dihydrolipoamide dehydrogenase binding protein (E3BP) combine to form a complex that plays a central role in the organization, regulation, and integration of catalytic reactions of PDC. However, the atomic structure and organization of the mammalian E2p/E3BP heterocomplex are unknown. Here, we report the structure of the recombinant dodecahedral core formed by the C-terminal inner-core/catalytic (IC) domain of human E2p determined at 3.1 Å resolution by cryo electron microscopy (cryoEM). The structure of the N-terminal fragment and four other surface areas of the human E2p IC domain exhibit significant differences from those of the other E2 crystal structures, which may have implications for the integration of E3BP in mammals. This structure also allowed us to obtain a homology model for the highly homologous IC domain of E3BP. Analysis of the interactions of human E2p or E3BP with their adjacent IC domains in the dodecahedron provides new insights into the organization of the E2p/E3BP heterocomplex and suggests a potential contribution by E3BP to catalysis in mammalian PDC.

更新日期：2018-04-02

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