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Structure of subcomplex Iβ of mammalian respiratory complex I leads to new supernumerary subunit assignments

DOI: 10.1073/pnas.1510577112 DOI Help

Authors: Jiapeng Zhu (MRC Human Nutrition Research) , Martin King (MRC Mitochondrial Biology Unit) , Minmin Yu (MMRC Laboratory of Molecular Biology) , Liron Klipcan (MRC Mitochondrial Biology Unit) , Andrew Leslie (MRC Laboratory of Molecular Biology) , Judy Hirst (MRC Mitochondrial Biology Unit)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 112 , PAGES 12087 - 12092

State: Published (Approved)
Published: September 2015

Abstract: Mitochondrial complex I (proton-pumping NADH:ubiquinone oxidoreductase) is an essential respiratory enzyme. Mammalian complex I contains 45 subunits: 14 conserved “core” subunits and 31 “supernumerary” subunits. The structure of Bos taurus complex I, determined to 5-Å resolution by electron cryomicroscopy, described the structure of the mammalian core enzyme and allowed the assignment of 14 supernumerary subunits. Here, we describe the 6.8-Å resolution X-ray crystallography structure of subcomplex Iβ, a large portion of the membrane domain of B. taurus complex I that contains two core subunits and a cohort of supernumerary subunits. By comparing the structures and composition of subcomplex Iβ and complex I, supported by comparisons with Yarrowia lipolytica complex I, we propose assignments for eight further supernumerary subunits in the structure. Our new assignments include two CHCH-domain containing subunits that contain disulfide bridges between CX9C motifs; they are processed by the Mia40 oxidative-folding pathway in the intermembrane space and probably stabilize the membrane domain. We also assign subunit B22, an LYR protein, to the matrix face of the membrane domain. We reveal that subunit B22 anchors an acyl carrier protein (ACP) to the complex, replicating the LYR protein–ACP structural module that was identified previously in the hydrophilic domain. Thus, we significantly extend knowledge of how the mammalian supernumerary subunits are arranged around the core enzyme, and provide insights into their roles in biogenesis and regulation.

Journal Keywords: CHCH domain electron transport chain LYR protein mitochondria NADH:ubiquinone oxidoreductase

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 22/12/2015 13:12

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