7PGE

copper transporter PcoB

Summary for 7PGE

• Entry DOI: 10.2210/pdb7pge/pdb
• Descriptor: Copper resistance protein B, (HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE, LAURYL DIMETHYLAMINE-N-OXIDE, ... (5 entities in total)
• Functional Keywords: transporter, transport protein
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 24969.86

Authors

Li, P.,Gourdon, P.E. (deposition date: 2021-08-13, release date: 2022-07-06, Last modification date: 2024-06-19)

Primary citation

Li, P.,Nayeri, N.,Gorecki, K.,Becares, E.R.,Wang, K.,Mahato, D.R.,Andersson, M.,Abeyrathna, S.S.,Lindkvist-Petersson, K.,Meloni, G.,Missel, J.W.,Gourdon, P.
PcoB is a defense outer membrane protein that facilitates cellular uptake of copper.
Protein Sci., 31:e4364-e4364, 2022

PubMed Abstract: 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.

PubMed: 35762724
DOI: 10.1002/pro.4364

Experimental method

X-RAY DIFFRACTION (2 Å)