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Acquisition of ionic copper by the bacterial outer membrane protein OprC through a novel binding site

DOI: 10.1371/journal.pbio.3001446 DOI Help

Authors: Satya Prathyusha Bhamidimarri (Newcastle University) , Tessa R. Young (Durham University) , Muralidharan Shanmugam (University of Manchester) , Sandra Soderholm (University of Basel) , Arnaud Basle (Newcastle University) , Dirk Bumann (University of Basel) , Bert Van Den Berg (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Biology , VOL 19

State: Published (Approved)
Published: November 2021
Diamond Proposal Number(s): 9948 , 13587 , 18598

Open Access Open Access

Abstract: Copper, while toxic in excess, is an essential micronutrient in all kingdoms of life due to its essential role in the structure and function of many proteins. Proteins mediating ionic copper import have been characterised in detail for eukaryotes, but much less so for prokaryotes. In particular, it is still unclear whether and how gram-negative bacteria acquire ionic copper. Here, we show that Pseudomonas aeruginosa OprC is an outer membrane, TonB-dependent transporter that is conserved in many Proteobacteria and which mediates acquisition of both reduced and oxidised ionic copper via an unprecedented CxxxM-HxM metal binding site. Crystal structures of wild-type and mutant OprC variants with silver and copper suggest that acquisition of Cu(I) occurs via a surface-exposed “methionine track” leading towards the principal metal binding site. Together with whole-cell copper quantitation and quantitative proteomics in a murine lung infection model, our data identify OprC as an abundant component of bacterial copper biology that may enable copper acquisition under a wide range of conditions.

Journal Keywords: Pseudomonas aeruginosa; Methionine; Crystal structure; Silver; Crystallization; Crystals; Zinc; Copper

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 16/11/2021 19:33


Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)