Cargando…

Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels

Cytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we h...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Weiwei, Gao, Yan, Tang, Yanting, Zhou, Xiaoting, Lai, Yuezheng, Zhou, Shan, Zhang, Yuying, Yang, Xiuna, Liu, Fengjiang, Guddat, Luke W., Wang, Quan, Rao, Zihe, Gong, Hongri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324918/
https://www.ncbi.nlm.nih.gov/pubmed/34330928
http://dx.doi.org/10.1038/s41467-021-24924-w
_version_ 1783731459933077504
author Wang, Weiwei
Gao, Yan
Tang, Yanting
Zhou, Xiaoting
Lai, Yuezheng
Zhou, Shan
Zhang, Yuying
Yang, Xiuna
Liu, Fengjiang
Guddat, Luke W.
Wang, Quan
Rao, Zihe
Gong, Hongri
author_facet Wang, Weiwei
Gao, Yan
Tang, Yanting
Zhou, Xiaoting
Lai, Yuezheng
Zhou, Shan
Zhang, Yuying
Yang, Xiuna
Liu, Fengjiang
Guddat, Luke W.
Wang, Quan
Rao, Zihe
Gong, Hongri
author_sort Wang, Weiwei
collection PubMed
description Cytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase.
format Online
Article
Text
id pubmed-8324918
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-83249182021-08-19 Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels Wang, Weiwei Gao, Yan Tang, Yanting Zhou, Xiaoting Lai, Yuezheng Zhou, Shan Zhang, Yuying Yang, Xiuna Liu, Fengjiang Guddat, Luke W. Wang, Quan Rao, Zihe Gong, Hongri Nat Commun Article Cytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase. Nature Publishing Group UK 2021-07-30 /pmc/articles/PMC8324918/ /pubmed/34330928 http://dx.doi.org/10.1038/s41467-021-24924-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Weiwei
Gao, Yan
Tang, Yanting
Zhou, Xiaoting
Lai, Yuezheng
Zhou, Shan
Zhang, Yuying
Yang, Xiuna
Liu, Fengjiang
Guddat, Luke W.
Wang, Quan
Rao, Zihe
Gong, Hongri
Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
title Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
title_full Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
title_fullStr Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
title_full_unstemmed Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
title_short Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
title_sort cryo-em structure of mycobacterial cytochrome bd reveals two oxygen access channels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324918/
https://www.ncbi.nlm.nih.gov/pubmed/34330928
http://dx.doi.org/10.1038/s41467-021-24924-w
work_keys_str_mv AT wangweiwei cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT gaoyan cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT tangyanting cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT zhouxiaoting cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT laiyuezheng cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT zhoushan cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT zhangyuying cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT yangxiuna cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT liufengjiang cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT guddatlukew cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT wangquan cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT raozihe cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels
AT gonghongri cryoemstructureofmycobacterialcytochromebdrevealstwooxygenaccesschannels