Structural Research of Electron Transport Chain Supercomplexes

Inquiry

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)

Protein	Organism	Method	Resolution	PDB Entry ID
Electron Transport Chain (ETC) Super Complex comprised of ETC complexes I, III, and IV, tight respirasome	Ovis aries	Cryo-EM single particle analysis	5.80 Å	5J4Z
Electron Transport Chain (ETC) Super Complex I+III2, closed class	Ovis aries	Cryo-EM single particle analysis	4.20 Å	6QBX
Electron Transport Chain (ETC) Super Complex comprised of ETC complexes I, III, and IV	Sus scrofa	Cryo-EM single particle analysis	5.40 Å	5GPN
Electron Transport Chain (ETC) Super Complex I1III2IV1	Sus scrofa	Cryo-EM single particle analysis	4.00 Å	5GUP
Respiratory supercomplex CIII2CIV2SOD2	Mycolicibacterium smegmatis	Cryo-EM single particle analysis	3.50 Å	6ADQ
Respiratory supercomplex CIII2CIV2 (expressed in Mycolicibacterium smegmatis)	Mycolicibacterium smegmatis	Cryo-EM single particle analysis	3.30 Å	6HWH
Respiratory supercomplex CIII2CIV2 with bound Telacebec (Q203)	Mycolicibacterium smegmatis	Cryo-EM single particle analysis	3.00 Å	7RH7
Electron Transport Chain (ETC) Super Complex III2IV	Saccharomyces cerevisiae	Cryo-EM single particle analysis	3.23 Å	6GIQ
Rcf1 protein involved in electron chain super-complex formation (expressed in E. coli)	Saccharomyces cerevisiae	Solution NMR	/	5NF8
Electron Transport Chain (ETC) Super Complex III2IV2 (expressed in Saccharomyces cerevisiae)	Saccharomyces cerevisiae	Cryo-EM single particle analysis	3.35 Å	6HU9
III2-IV(5B)1 respiratory supercomplex (expressed in Saccharomyces cerevisiae)	Saccharomyces cerevisiae	Cryo-EM single particle analysis	3.29 Å	6T15
Respiratory supercomplex Factor 2 (expressed in E. coli)	Saccharomyces cerevisiae	Solution NMR	/	6LUL
CIII2/CIV respiratory supercomplex	Saccharomyces cerevisiae	Cryo-EM single particle analysis	3.17 Å	6YMX
Respiratory supercomplex III2-IV	Vigna radiata	Cryo-EM single particle analysis	3.80 Å	7JRP
Respiratory supercomplex III2-IV. CIII2 (expressed in Rhodobacter capsulatus)	Rhodobacter capsulatus	Cryo-EM single particle analysis	3.30 Å	6XI0
Electron Transport Chain (ETC) hybrid Super Complex comprised of M. tuberculosis complexIII and M. smegmatis complexIV	Mycolicibacterium smegmatis	Cryo-EM single particle analysis	2.68 Å	7E1V
ETC Super Complex comprised of ETC complexes CIII2CIV, intermediate locked conformation	Mus musculus	Cryo-EM single particle analysis	3.60 Å	7O3E
III2-IV2 respiratory supercomplex (expressed in Corynebacterium glutamicum)	Corynebacterium glutamicum	Cryo-EM single particle analysis	2.90 Å	7Q21
III2-IV2 respiratory supercomplex, native (expressed in Corynebacterium glutamicum)	Corynebacterium glutamicum	Cryo-EM single particle analysis	3.10 Å	7QHO
Respiratory chain super-complex CI+III2	Tetrahymena thermophila	Cryo-EM single particle analysis	2.60 Å	7TGH
Electron Transport Chain (ETC) Super Complex, optimized supercomplex state1	Bos taurus	Cryo-EM single particle analysis	5.00 Å	7DGQ

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

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