title: Complex structure of cytochrome c-cytochrome c oxidase reveals a novel protein-protein interaction mode.
abstract: Mitochondrial cytochrome c oxidase (CcO) transfers electrons from cytochrome c (Cyt.c) to O2to generate H2O, a process coupled to proton pumping. To elucidate the mechanism of electron transfer, we determined the structure of the mammalian Cyt.c-CcO complex at 2.0-Å resolution and identified an electron transfer pathway from Cyt.c to CcO. The specific interaction between Cyt.c and CcO is stabilized by a few electrostatic interactions between side chains within a small contact surface area. Between the two proteins are three water layers with a long inter-molecular span, one of which lies between the other two layers without significant direct interaction with either protein. Cyt.c undergoes large structural fluctuations, using the interacting regions with CcO as a fulcrum. These features of the protein-protein interaction at the docking interface represent the first known example of a new class of protein-protein interaction, which we term "soft and specific". This interaction is likely to contribute to the rapid association/dissociation of the Cyt.c-CcO complex, which facilitates the sequential supply of four electrons for the O2reduction reaction.
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan shinzawa@sci.u-hyogo.ac.jp tsuki@protein.osaka-u.ac.jp.
authors.forename: Kyoko
authors.identifier: 0000-0002-4571-2218
authors.initials: K
authors.lastname: Shinzawa-Itoh
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Baba
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Aoe
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Shimada
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamashita
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kang
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tateno
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yoshikawa
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan shinzawa@sci.u-hyogo.ac.jp tsuki@protein.osaka-u.ac.jp.|Institute for Protein Research, Osaka University, Suita, Osaka, Japan.|JST, CREST, Kawaguchi, Saitama, Japan.
authors.forename: Tomitake
authors.initials: T
authors.lastname: Tsukihara
mesh_terms: D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism*; D006736:Horses; D008954:Models, Biological; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D045304:Cytochromes c; D003576:Electron Transport Complex IV; D010100:Oxygen
keywords: X‐ray crystallography; cytochrome c; cytochrome c oxidase; electron transfer complex; protein–protein interaction