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

TitleStructure of subcomplex Iβ of mammalian respiratory complex I leads to new supernumerary subunit assignments.
Publication TypeJournal Article
Year of Publication2015
AuthorsZhu, J, King, MS, Yu, M, Klipcan, L, Leslie, AGW, Hirst, J
JournalProc Natl Acad Sci U S A
Date Published2015 Sep 29
KeywordsAnimals, Cattle, Cryoelectron Microscopy, Electron Transport Complex I, Models, Molecular, Protein Conformation, Protein Subunits, Yarrowia

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.1510577112
PubMed ID26371297
PubMed Central IDPMC4593082
Grant ListU105184325 / / Medical Research Council / United Kingdom
U105663141 / / Medical Research Council / United Kingdom