Structure of Escherichia coli respiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation
- VIB-VUB, Belgium
Abstract
Respiratory complex I is a multi-subunit membrane protein complex that reversibly couples NADH oxidation and ubiquinone reduction with proton translocation against trans-membrane potential. Complex I from Escherichia coli is among the best functionally characterized complexes, but its structure remains unknown, hindering further mechanistic studies to understand the enzyme coupling mechanism. Here we describe the single particle cryo-electron microscopy (cryo-EM) structure of the entire catalytically active E. coli complex I reconstituted into lipid nanodiscs. The structure of this mesophilic bacterial complex I displays highly dynamic connection between the peripheral and membrane domains. The peripheral domain assembly is stabilized by unique terminal extensions and an insertion loop. The membrane domain structure reveals novel dynamic features. Unusual conformation of the conserved interface between the peripheral and membrane domains suggests an uncoupled conformation of the complex. Considering constraints imposed by the structural data we suggest a new simple hypothetical coupling mechanism for the molecular machine.
Data availability
Cryo-EM density maps and atomic models are deposited into the PDB and EMDB databases with the following accession codes: cytoplasmic domain (PDB ID: 7NZ1, EMD-12661), membrane domain (PDB ID: 7NYH, EMD-12652), entire complex conformation 1 (PDB ID: 7NYR, EMD-12653), conformation 2 (PDB ID: 7NYU,EMD-12654), conformation 3 (PDB ID: 7NYV, EMD-12655).
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Respiratory complex I from Escherichia coli - focused refinement of cytoplasmic armElectron Microscopy Data Bank ID EMD-12661.
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Respiratory complex I from Escherichia coli - focused refinement of membrane armElectron Microscopy Data Bank ID EMD-12652.
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Respiratory complex I from Escherichia coli - conformation 1Electron Microscopy Data Bank ID EMD-12653.
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Respiratory complex I from Escherichia coli - conformation 2Electron Microscopy Data Bank ID EMD-12654.
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Respiratory complex I from Escherichia coli - conformation 3Electron Microscopy Data Bank ID EMD-12655.
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Respiratory complex I from Escherichia coli - focused refinement of cytoplasmic armRCSB Protein Data Bank ID 7NZ1.
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Respiratory complex I from Escherichia coli - focused refinement of membrane armRCSB Protein Data Bank ID 7NYH.
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Respiratory complex I from Escherichia coli - conformation 1RCSB Protein Data Bank ID 7NYR.
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Respiratory complex I from Escherichia coli - conformation 2RCSB Protein Data Bank ID 7NYU.
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Respiratory complex I from Escherichia coli - conformation 3RCSB Protein Data Bank ID 7NYV.
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Crystal structure of the entire respiratory complex I from Thermus thermophilusRCSB Protein Data Bank ID 4HEA.
Article and author information
Author details
Funding
Fonds Wetenschappelijk Onderzoek (G0H5916N)
- Rouslan G Efremov
Fonds Wetenschappelijk Onderzoek (G.0266.15N)
- Rouslan G Efremov
H2020 European Research Council (726436)
- Rouslan G Efremov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Efremov & Kolata
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structure of Escherichia coli respiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation
eLife 10:e68710.
https://doi.org/10.7554/eLife.68710
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