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PcoB is a defense outer membrane protein that facilitates cellular uptake of copper
Copper (Cu) is one of the most abundant trace metals in all organisms, involved in a plethora of cellular processes. Yet elevated concentrations of the element are harmful, and interestingly prokaryotes are more sensitive for environmental Cu stress than humans. Various transport systems are present...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210255/ https://www.ncbi.nlm.nih.gov/pubmed/35762724 http://dx.doi.org/10.1002/pro.4364 |
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author | Li, Ping Nayeri, Niloofar Górecki, Kamil Becares, Eva Ramos Wang, Kaituo Mahato, Dhani Ram Andersson, Magnus Abeyrathna, Sameera S. Lindkvist‐Petersson, Karin Meloni, Gabriele Missel, Julie Winkel Gourdon, Pontus |
author_facet | Li, Ping Nayeri, Niloofar Górecki, Kamil Becares, Eva Ramos Wang, Kaituo Mahato, Dhani Ram Andersson, Magnus Abeyrathna, Sameera S. Lindkvist‐Petersson, Karin Meloni, Gabriele Missel, Julie Winkel Gourdon, Pontus |
author_sort | Li, Ping |
collection | PubMed |
description | Copper (Cu) is one of the most abundant trace metals in all organisms, involved in a plethora of cellular processes. Yet elevated concentrations of the element are harmful, and interestingly prokaryotes are more sensitive for environmental Cu stress than humans. Various transport systems are present to maintain intracellular Cu homeostasis, including the prokaryotic plasmid‐encoded multiprotein pco operon, which is generally assigned as a defense mechanism against elevated Cu concentrations. Here we structurally and functionally characterize the outer membrane component of the Pco system, PcoB, recovering a 2.0 Å structure, revealing a classical β‐barrel architecture. Unexpectedly, we identify a large opening on the extracellular side, linked to a considerably electronegative funnel that becomes narrower towards the periplasm, defining an ion‐conducting pathway as also supported by metal binding quantification via inductively coupled plasma mass spectrometry and molecular dynamics (MD) simulations. However, the structure is partially obstructed towards the periplasmic side, and yet flux is permitted in the presence of a Cu gradient as shown by functional characterization in vitro. Complementary in vivo experiments demonstrate that isolated PcoB confers increased sensitivity towards Cu. Aggregated, our findings indicate that PcoB serves to permit Cu import. Thus, it is possible the Pco system physiologically accumulates Cu in the periplasm as a part of an unorthodox defense mechanism against metal stress. These results point to a previously unrecognized principle of maintaining Cu homeostasis and may as such also assist in the understanding and in efforts towards combatting bacterial infections of Pco‐harboring pathogens. |
format | Online Article Text |
id | pubmed-9210255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92102552022-08-26 PcoB is a defense outer membrane protein that facilitates cellular uptake of copper Li, Ping Nayeri, Niloofar Górecki, Kamil Becares, Eva Ramos Wang, Kaituo Mahato, Dhani Ram Andersson, Magnus Abeyrathna, Sameera S. Lindkvist‐Petersson, Karin Meloni, Gabriele Missel, Julie Winkel Gourdon, Pontus Protein Sci Full‐length Papers Copper (Cu) is one of the most abundant trace metals in all organisms, involved in a plethora of cellular processes. Yet elevated concentrations of the element are harmful, and interestingly prokaryotes are more sensitive for environmental Cu stress than humans. Various transport systems are present to maintain intracellular Cu homeostasis, including the prokaryotic plasmid‐encoded multiprotein pco operon, which is generally assigned as a defense mechanism against elevated Cu concentrations. Here we structurally and functionally characterize the outer membrane component of the Pco system, PcoB, recovering a 2.0 Å structure, revealing a classical β‐barrel architecture. Unexpectedly, we identify a large opening on the extracellular side, linked to a considerably electronegative funnel that becomes narrower towards the periplasm, defining an ion‐conducting pathway as also supported by metal binding quantification via inductively coupled plasma mass spectrometry and molecular dynamics (MD) simulations. However, the structure is partially obstructed towards the periplasmic side, and yet flux is permitted in the presence of a Cu gradient as shown by functional characterization in vitro. Complementary in vivo experiments demonstrate that isolated PcoB confers increased sensitivity towards Cu. Aggregated, our findings indicate that PcoB serves to permit Cu import. Thus, it is possible the Pco system physiologically accumulates Cu in the periplasm as a part of an unorthodox defense mechanism against metal stress. These results point to a previously unrecognized principle of maintaining Cu homeostasis and may as such also assist in the understanding and in efforts towards combatting bacterial infections of Pco‐harboring pathogens. John Wiley & Sons, Inc. 2022-06-21 2022-07 /pmc/articles/PMC9210255/ /pubmed/35762724 http://dx.doi.org/10.1002/pro.4364 Text en © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full‐length Papers Li, Ping Nayeri, Niloofar Górecki, Kamil Becares, Eva Ramos Wang, Kaituo Mahato, Dhani Ram Andersson, Magnus Abeyrathna, Sameera S. Lindkvist‐Petersson, Karin Meloni, Gabriele Missel, Julie Winkel Gourdon, Pontus PcoB is a defense outer membrane protein that facilitates cellular uptake of copper |
title |
PcoB is a defense outer membrane protein that facilitates cellular uptake of copper |
title_full |
PcoB is a defense outer membrane protein that facilitates cellular uptake of copper |
title_fullStr |
PcoB is a defense outer membrane protein that facilitates cellular uptake of copper |
title_full_unstemmed |
PcoB is a defense outer membrane protein that facilitates cellular uptake of copper |
title_short |
PcoB is a defense outer membrane protein that facilitates cellular uptake of copper |
title_sort | pcob is a defense outer membrane protein that facilitates cellular uptake of copper |
topic | Full‐length Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210255/ https://www.ncbi.nlm.nih.gov/pubmed/35762724 http://dx.doi.org/10.1002/pro.4364 |
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