Structural Research of Electron Transport Chain Complex I

Inquiry

The electron transport chain (ETC) is a fundamental process in aerobic respiration that produces ATP, the primary source of energy for living organisms. Among its key components is respiratory complex I, a large and intricate membrane protein complex responsible for the transfer of electrons from NADH to ubiquinone. In recent years, significant advances have been made in the structural research of complex I, which have contributed to our understanding of its biological function. For instance, the application of single-particle cryo-electron microscopy (cryo-EM) to study the catalytically active E. coli complex I, reconstituted into lipid nanodiscs, has revealed new information on the coupling mechanism of the enzyme. The structural analysis indicates a highly dynamic connection between the peripheral and membrane domains of the complex, with the peripheral domain assembly stabilized by unique terminal extensions and an insertion loop. Additionally, the membrane domain structure has unveiled novel dynamic features. Notably, the unconventional conformation of the conserved interface between the peripheral and membrane domains suggests an uncoupled state of the complex. The integration of these structural data has allowed for the proposal of a new simple hypothetical coupling mechanism for this molecular machine. Moreover, the determination of the peripheral arm structure at a resolution of 2.1 Å and that of the membrane domain at 3.7 Å has provided crucial insights into the structure and function of this complex, enhancing our knowledge of the respiratory chain in living systems.

Figure 1. Architecture of E. coli respiratory complex I. (Kolata P, et al., 2021)

Protein	Organism	Method	Resolution	PDB Entry ID
Complex I membrane domain	Escherichia coli	X-ray diffraction	3.90 Å	3M9C
Complex I membrane domain	Escherichia coli	X-ray diffraction	3.00 Å	3RKO
Complex I complete, focused refinement of cytoplasmic arm	Escherichia coli	Cryo-EM single particle analysis	2.10 Å	7NZ1
NADH quinone oxidoreductase hydrophilic arm (expressed in E. coli)	Escherichia coli	Cryo-EM single particle analysis	2.73 Å	7AWT
Respiratory Complex I, DDM-purified, Apo, Resting state	Escherichia coli	Cryo-EM single particle analysis	3.60 Å	7P62
Complex I complete	Thermus thermophilus HB8	X-ray diffraction	4.50 Å	3M9S
Complex I complete	Thermus thermophilus HB8	X-ray diffraction	3.30 Å	4HEA
Complex I soluble domain, oxidized (4 mol/ASU)	Thermus thermophilus HB8	X-ray diffraction	3.30 Å	2FUG
Complex I soluble domain, oxidized (2 mol/ASU)	Thermus thermophilus HB8	X-ray diffraction	3.10 Å	3I9V
Complex I complete	Thermus thermophilus	X-ray diffraction	3.11 Å	6Y11
Na+-pumping NADH-ubiquinone oxidoreductase, State 1 (expressed in Vibrio cholerae)	Vibrio cholerae O395	Cryo-EM single particle analysis	3.10 Å	7XK3
Respiratory Complex I	Bos taurus	Cryo-EM single particle analysis	4.95 Å	4UQ8
Respiratory Complex I (class 1 conformation)	Bos taurus	Cryo-EM single particle analysis	4.27 Å	5LDW
Respiratory Complex I, deactive state	Bos taurus	Cryo-EM single particle analysis	4.13 Å	5O31
Respiratory Complex I in lipid nanodisc, Active-Q10	Bos taurus	Cryo-EM single particle analysis	2.84 Å	7QSK
Respiratory Complex I in the presence of IM1761092, active class i	Bos taurus	Cryo-EM single particle analysis	2.30 Å	7R41
Respiratory Complex I, active state complex from Q10 dataset	Sus scrofa	Cryo-EM single particle analysis	2.90 Å	7V2C
Respiratory Complex I	Ovis aries	Cryo-EM single particle analysis	3.90 Å	5LNK
Respiratory Complex I, pH5.5, Open state	Ovis aries	Cryo-EM single particle analysis	3.25 Å	7ZDJ
Respiratory Complex I, active state	Mus musculus	Cryo-EM single particle analysis	3.30 Å	6G2J
Respiratory Complex I with inhibitor piericidin A	Mus musculus	Cryo-EM single particle analysis	3.00 Å	6ZTQ
Respiratory Complex I, deactive state	Mus musculus	Cryo-EM single particle analysis	3.17 Å	7AK5
Respiratory Complex I inhibited by IACS-2858	Mus musculus	Cryo-EM single particle analysis	3.04 Å	7B93
Respiratory Complex I inhibited by acetogenin	Mus musculus	Cryo-EM single particle analysis	3.40 Å	7PSA
Mitochondrial Complex I	Yarrowia lipolytica	X-ray diffraction	3.60 Å	4WZ7
Mitochondrial Complex I in deactive form	Yarrowia lipolytica	Cryo-EM single particle analysis	4.32 Å	6GCS
Mitochondrial Complex I	Yarrowia lipolytica	Cryo-EM single particle analysis	3.20 Å	6RFR
Mitochondrial Complex I (expressed in Yarrowia lipolytica)	Yarrowia lipolytica	Cryo-EM single particle analysis	2.70 Å	6YJ4
Mitochondrial Complex I, F89A mutant	Yarrowia lipolytica	Cryo-EM single particle analysis	2.96 Å	6Y79
Membrane-bound hydrogenase ancient respiratory system (expressed in Pyrococcus furiosus)	Pyrococcus furiosus COM1	Cryo-EM single particle analysis	3.70 Å	6CFW
Complex I-like photosynthetic NAD(P)H, NDH-Fd structure (expressed in E. coli)	Thermosynechococcus vestitus BP-1	Cryo-EM single particle analysis	3.00 Å	6KHI
Ferredoxin (FD)-NDH-1L complex (expressed in E. coli)	Thermosynechococcus vestitus BP-1	Cryo-EM single particle analysis	3.20 Å	6L7O
Mrp ancient cation/proton antiporter complex (expressed in E. coli)	Anoxybacillus flavithermus WK1	Cryo-EM single particle analysis	2.98 Å	6Z16
Formate hydrogenlyase complex, anaerobic preparation, without formate dehydrogenase H (expressed in E. coli)	Escherichia coli	Cryo-EM single particle analysis	2.60 Å	7Z0S
Mitochondrial complex I* from mung bean	Vigna radiata	Cryo-EM single particle analysis	3.90 Å	6X89
Mitochondrial Complex I	Brassica oleracea	Cryo-EM single particle analysis	3.70 Å	7A23
Mitochondrial Complex I: native complex, closed	Ovis aries	Cryo-EM single particle analysis	3.80 Å	6ZKO
Mitochondrial Complex I, complete composition	Arabidopsis thaliana	Cryo-EM single particle analysis	3.41 Å	7ARB
Mitochondrial Complex I, complete composition	Polytomella sp. Pringsheim	Cryo-EM single particle analysis	3.11 Å	7ARD

Table 1. Structural Research of Electron Transport Chain Complex I.

At Creative Biostructure, we specialize in analyzing the structure of membrane proteins (including electron transport chain complex I). Our team of highly skilled scientists utilizes various cutting-edge techniques such as cryo-EM, X-ray crystallography, and nuclear magnetic resonance (NMR) spectroscopy to obtain high-resolution images and detailed structural information. We provide a comprehensive range of services, including sample preparation, data collection and analysis, and structure determination, tailored to meet the specific needs of our clients. Our state-of-the-art facilities and equipment, combined with our extensive experience in membrane protein research, ensure timely and cost-effective delivery of high-quality results.

Whether you need high-resolution structures of electron transport chain complex I for research purposes or detailed structural information for drug development, we have the expertise and support to help you achieve your goals. Please feel free to contact us to learn more about our membrane protein structural analysis services. Our team of expert scientists is always available to address your inquiries and assist you in accomplishing your research objectives.

References

Kolata P, Efremov R G. Structure of Escherichia coli respiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation. Elife. 2021, 10: e68710.
Gutiérrez-Fernández J, et al. Key role of quinone in the mechanism of respiratory complex I. Nature Communications. 2020, 11(1): 4135.
Bridges H R, et al. Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides. Science. 2023, 379(6630): 351-357.