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Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons

Cytochrome c oxidase (CcO) reduces O(2) in the O(2)-reduction site by sequential four-electron donations through the low-potential metal sites (Cu(A) and Fe(a)). Redox-coupled X-ray crystal structural changes have been identified at five distinct sites including Asp(51), Arg(438), Glu(198), the hydr...

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Autores principales: Shimada, Atsuhiro, Baba, Jumpei, Nagao, Shuhei, Shinzawa-Itoh, Kyoko, Yamashita, Eiki, Muramoto, Kazumasa, Tsukihara, Tomitake, Yoshikawa, Shinya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598403/
https://www.ncbi.nlm.nih.gov/pubmed/37742916
http://dx.doi.org/10.1016/j.jbc.2023.105277
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author Shimada, Atsuhiro
Baba, Jumpei
Nagao, Shuhei
Shinzawa-Itoh, Kyoko
Yamashita, Eiki
Muramoto, Kazumasa
Tsukihara, Tomitake
Yoshikawa, Shinya
author_facet Shimada, Atsuhiro
Baba, Jumpei
Nagao, Shuhei
Shinzawa-Itoh, Kyoko
Yamashita, Eiki
Muramoto, Kazumasa
Tsukihara, Tomitake
Yoshikawa, Shinya
author_sort Shimada, Atsuhiro
collection PubMed
description Cytochrome c oxidase (CcO) reduces O(2) in the O(2)-reduction site by sequential four-electron donations through the low-potential metal sites (Cu(A) and Fe(a)). Redox-coupled X-ray crystal structural changes have been identified at five distinct sites including Asp(51), Arg(438), Glu(198), the hydroxyfarnesyl ethyl group of heme a, and Ser(382), respectively. These sites interact with the putative proton-pumping H-pathway. However, the metal sites responsible for each structural change have not been identified, since these changes were detected as structural differences between the fully reduced and fully oxidized CcOs. Thus, the roles of these structural changes in the CcO function are yet to be revealed. X-ray crystal structures of cyanide-bound CcOs under various oxidation states showed that the O(2)-reduction site controlled only the Ser(382)-including site, while the low-potential metal sites induced the other changes. This finding indicates that these low-potential site-inducible structural changes are triggered by sequential electron-extraction from the low-potential sites by the O(2)-reduction site and that each structural change is insensitive to the oxidation and ligand-binding states of the O(2)-reduction site. Because the proton/electron coupling efficiency is constant (1:1), regardless of the reaction progress in the O(2)-reduction site, the structural changes induced by the low-potential sites are assignable to those critically involved in the proton pumping, suggesting that the H-pathway, facilitating these low-potential site-inducible structural changes, pumps protons. Furthermore, a cyanide-bound CcO structure suggests that a hypoxia-inducible activator, Higd1a, activates the O(2)-reduction site without influencing the electron transfer mechanism through the low-potential sites, kinetically confirming that the low-potential sites facilitate proton pump.
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spelling pubmed-105984032023-10-26 Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons Shimada, Atsuhiro Baba, Jumpei Nagao, Shuhei Shinzawa-Itoh, Kyoko Yamashita, Eiki Muramoto, Kazumasa Tsukihara, Tomitake Yoshikawa, Shinya J Biol Chem Research Article Cytochrome c oxidase (CcO) reduces O(2) in the O(2)-reduction site by sequential four-electron donations through the low-potential metal sites (Cu(A) and Fe(a)). Redox-coupled X-ray crystal structural changes have been identified at five distinct sites including Asp(51), Arg(438), Glu(198), the hydroxyfarnesyl ethyl group of heme a, and Ser(382), respectively. These sites interact with the putative proton-pumping H-pathway. However, the metal sites responsible for each structural change have not been identified, since these changes were detected as structural differences between the fully reduced and fully oxidized CcOs. Thus, the roles of these structural changes in the CcO function are yet to be revealed. X-ray crystal structures of cyanide-bound CcOs under various oxidation states showed that the O(2)-reduction site controlled only the Ser(382)-including site, while the low-potential metal sites induced the other changes. This finding indicates that these low-potential site-inducible structural changes are triggered by sequential electron-extraction from the low-potential sites by the O(2)-reduction site and that each structural change is insensitive to the oxidation and ligand-binding states of the O(2)-reduction site. Because the proton/electron coupling efficiency is constant (1:1), regardless of the reaction progress in the O(2)-reduction site, the structural changes induced by the low-potential sites are assignable to those critically involved in the proton pumping, suggesting that the H-pathway, facilitating these low-potential site-inducible structural changes, pumps protons. Furthermore, a cyanide-bound CcO structure suggests that a hypoxia-inducible activator, Higd1a, activates the O(2)-reduction site without influencing the electron transfer mechanism through the low-potential sites, kinetically confirming that the low-potential sites facilitate proton pump. American Society for Biochemistry and Molecular Biology 2023-09-22 /pmc/articles/PMC10598403/ /pubmed/37742916 http://dx.doi.org/10.1016/j.jbc.2023.105277 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Shimada, Atsuhiro
Baba, Jumpei
Nagao, Shuhei
Shinzawa-Itoh, Kyoko
Yamashita, Eiki
Muramoto, Kazumasa
Tsukihara, Tomitake
Yoshikawa, Shinya
Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons
title Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons
title_full Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons
title_fullStr Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons
title_full_unstemmed Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons
title_short Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons
title_sort crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer h-pathway pumps protons
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598403/
https://www.ncbi.nlm.nih.gov/pubmed/37742916
http://dx.doi.org/10.1016/j.jbc.2023.105277
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