Structural Research of Electron Transport Chain Supercomplexes

The enzymes within the mitochondrial electron transport chain play a critical role in cellular metabolism. Although they are active when isolated, they form supercomplexes in vivo, the exact function of which is currently under debate.

Cryo-electron microscopy (cryo-EM) has significantly advanced structural biology, providing near-atomic resolution visualization of large macromolecular complexes. Recently, cryo-EM was used to visualize a respiratory supercomplex from Mycobacterium smegmatis, a bacterium causing tuberculosis. The structure consists of 20 subunits that associate to form the complex, including a CIII dimer, flanked by individual CIV subunits. Fused c-type cytochrome domains bridge and mediate electron transfer from CIII to CIV. Additionally, the structure revealed three previously unknown subunits, contributing to the supercomplex stability, and the presence of superoxide dismutase (SOD), responsible for the detoxification of superoxide formed by CIII.

In mammals, there are three types of supercomplexes, CICIII₂, CIII₂CIV_1-2 and CICIII₂CIV (respirasome), which differ in their organizations. Recently, the structures of mammalian (ovine and mouse) CIII₂CIV and its assembly intermediates in distinct conformations were presented. The assembly of CIII₂CIV from the CIII₂ precursor to the final CIII₂CIV conformation was elucidated. These findings provide valuable insights into the assembly and organization of the respiratory supercomplexes.

Figure 1. Structure of mycobacterial respiratory supercomplex CIII₂CIV₂SOD₂. (Gong H, et al., 2018)

Table 1. Structural Research of Electron Transport Chain Supercomplexes.

The increasing interest in the structure and function of supercomplexes has led to a demand for high-quality structural analysis services. Cryo-EM is a powerful technique for visualizing these large macromolecular complexes, but it requires specialized expertise and equipment. Creative Biostructure is a leading provider of protein structural analysis services, offering cryo-EM, X-ray crystallography, and NMR spectroscopy services for a wide range of biological macromolecules, such as electron transport chain supercomplexes. We provide comprehensive cryo-EM services, from sample preparation to data collection and processing, to generate high-resolution structures of complex biological systems.

If you are keen on delving into the structural research of supercomplexes and want to know more about the services we provide, please feel free to contact us. Our team is available round the clock to address your research requirements and offer optimal solutions for your project.

References

1. Gong H, et al. An electron transfer path connects subunits of a mycobacterial respiratory supercomplex. Science. 2018, 362(6418): eaat8923.
2. Vercellino I, Sazanov L A. Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV. Nature. 2021, 598(7880): 364-367.
3. Zhou L, et al. Structures of Tetrahymena's respiratory chain reveal the diversity of eukaryotic core metabolism. Science. 2022, 376(6595): 831-839.