PMID- 27979921 OWN - NLM STAT- MEDLINE DCOM- 20170703 LR - 20210109 IS - 1460-2075 (Electronic) IS - 0261-4189 (Print) IS - 0261-4189 (Linking) VI - 36 IP - 3 DP - 2017 Feb 1 TI - Complex structure of cytochrome c-cytochrome c oxidase reveals a novel protein-protein interaction mode. PG - 291-300 LID - 10.15252/embj.201695021 [doi] AB - Mitochondrial cytochrome c oxidase (CcO) transfers electrons from cytochrome c (Cyt.c) to O(2) to generate H(2)O, 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-A 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 O(2) reduction reaction. CI - (c) 2016 The Authors. Published under the terms of the CC BY 4.0 license. FAU - Shimada, Satoru AU - Shimada S AD - Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan. FAU - Shinzawa-Itoh, Kyoko AU - Shinzawa-Itoh K AUID- ORCID: 0000-0002-4571-2218 AD - 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. FAU - Baba, Junpei AU - Baba J AD - Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan. FAU - Aoe, Shimpei AU - Aoe S AD - Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan. FAU - Shimada, Atsuhiro AU - Shimada A AD - Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan. FAU - Yamashita, Eiki AU - Yamashita E AD - Institute for Protein Research, Osaka University, Suita, Osaka, Japan. FAU - Kang, Jiyoung AU - Kang J AD - Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan. FAU - Tateno, Masaru AU - Tateno M AD - Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan. FAU - Yoshikawa, Shinya AU - Yoshikawa S AD - Picobiology Institute, Graduate School of Life Science, University of Hyogo, Akoh, Hyogo, Japan. FAU - Tsukihara, Tomitake AU - Tsukihara T AD - 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. AD - Institute for Protein Research, Osaka University, Suita, Osaka, Japan. AD - JST, CREST, Kawaguchi, Saitama, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161215 PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 059QF0KO0R (Water) RN - 9007-43-6 (Cytochromes c) RN - EC 1.9.3.1 (Electron Transport Complex IV) RN - S88TT14065 (Oxygen) SB - IM CIN - EMBO J. 2017 Feb 1;36(3):250-251. PMID: 28087581 MH - Animals MH - Cattle MH - Crystallography, X-Ray MH - Cytochromes c/*chemistry/*metabolism MH - Electron Transport MH - Electron Transport Complex IV/*chemistry/*metabolism MH - Horses MH - Models, Biological MH - Models, Molecular MH - Oxygen/metabolism MH - Protein Binding MH - Protein Conformation MH - Water/metabolism PMC - PMC5286356 OTO - NOTNLM OT - X-ray crystallography OT - cytochrome c OT - cytochrome c oxidase OT - electron transfer complex OT - protein-protein interaction EDAT- 2016/12/17 06:00 MHDA- 2017/07/04 06:00 PMCR- 2016/12/15 CRDT- 2016/12/17 06:00 PHST- 2016/06/16 00:00 [received] PHST- 2016/10/21 00:00 [revised] PHST- 2016/11/16 00:00 [accepted] PHST- 2016/12/17 06:00 [pubmed] PHST- 2017/07/04 06:00 [medline] PHST- 2016/12/17 06:00 [entrez] PHST- 2016/12/15 00:00 [pmc-release] AID - embj.201695021 [pii] AID - EMBJ201695021 [pii] AID - 10.15252/embj.201695021 [doi] PST - ppublish SO - EMBO J. 2017 Feb 1;36(3):291-300. doi: 10.15252/embj.201695021. Epub 2016 Dec 15.