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Structure of mammalian respiratory complex I

Date:
August 12, 2016
Source:
MRC Mitochondrial Biology Unit
Summary:
New research outlines discoveries on the complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane.
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Structure of respiratory complex I.
Credit: Image courtesy of MRC Mitochondrial Biology Unit

Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane. Mammalian complex I contains 45 subunits, comprising 14 core subunits that house the catalytic machinery (and are conserved from bacteria to humans) and a mammalian-specific cohort of 31 supernumerary subunits.

Knowledge of the structures and functions of the supernumerary subunits is fragmentary.

Here we describe a 4.2-Å resolution single-particle electron cryomicroscopy structure of complex I from Bos taurus. We have located and modelled all 45 subunits, including the 31 supernumerary subunits, to provide the entire structure of the mammalian complex. Computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally dynamic regions and match biochemical descriptions of the 'active-to-de-active' enzyme transition that occurs during hypoxia.

Our structures therefore provide a foundation for understanding complex I assembly and the effects of mutations that cause clinically relevant complex I dysfunctions, give insights into the structural and functional roles of the supernumerary subunits and reveal new information on the mechanism and regulation of catalysis.


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Materials provided by MRC Mitochondrial Biology Unit. Note: Content may be edited for style and length.


Journal Reference:

  1. Jiapeng Zhu, Kutti R. Vinothkumar, Judy Hirst. Structure of mammalian respiratory complex I. Nature, 2016; DOI: 10.1038/nature19095

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MRC Mitochondrial Biology Unit. "Structure of mammalian respiratory complex I." ScienceDaily. ScienceDaily, 12 August 2016. <www.sciencedaily.com/releases/2016/08/160812103840.htm>.
MRC Mitochondrial Biology Unit. (2016, August 12). Structure of mammalian respiratory complex I. ScienceDaily. Retrieved May 25, 2017 from www.sciencedaily.com/releases/2016/08/160812103840.htm
MRC Mitochondrial Biology Unit. "Structure of mammalian respiratory complex I." ScienceDaily. www.sciencedaily.com/releases/2016/08/160812103840.htm (accessed May 25, 2017).

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