PcoB is a defense outer membrane protein that facilitates cellular uptake of copper

Ping Li, Niloofar Nayeri, Kamil Górecki, Eva Ramos Becares, Kaituo Wang, Dhani Ram Mahato, Magnus Andersson, Sameera S. Abeyrathna, Karin Lindkvist-Petersson, Gabriele Meloni, Julie Winkel Missel, Pontus Gourdon

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere4364
JournalProtein Science
Issue number7
Publication statusPublished - 2022 Jul

Subject classification (UKÄ)

  • Medical Biotechnology

Free keywords

  • gut microbiota
  • outer membrane protein structure
  • PcoB


Dive into the research topics of 'PcoB is a defense outer membrane protein that facilitates cellular uptake of copper'. Together they form a unique fingerprint.

Cite this