Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 39, Pages 12087-12092Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1510577112
Keywords
CHCH domain; electron transport chain; LYR protein; mitochondria; NADH:ubiquinone oxidoreductase
Categories
Funding
- Medical Research Council [U105663141, U105184325]
- MRC [MC_U105184325, MC_U105663141] Funding Source: UKRI
- Medical Research Council [MC_U105184325, MC_U105663141] Funding Source: researchfish
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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-angstrom 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-angstrom resolution X-ray crystallography structure of subcomplex I beta, 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 I beta 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.
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