Atypical features of the disordered N-terminal region of a bacterial outer membrane copper transporter.

ABSTRACT: Metals like copper (Cu), zinc, and nickel exhibit dual nature, necessitating a tight regulation of their cellular homeostasis to meet physiological demands while preventing toxicity. In bacteria, metal homeostasis involves inner membrane P-type ATPases and ABC transporters, envelope-spanning tripartite efflux pumps, and outer membrane pore-forming proteins. Four decades ago, the outer membrane β-barrel protein PcoB was shown to provide an additional layer of copper resistance in an E. coli strain isolated from the gut of swine fed with Cu supplements. Interestingly, most PcoB homologs contain a poorly conserved disordered N-terminal domain (NTD) rich in histidine and methionine residues, which are commonly associated with copper coordination in cuproproteins. This suggests a potential role for the NTD in PcoB-mediated copper efflux. We previously demonstrated that the free-living bacterium Caulobacter vibroides primarily relies on PcoB for copper homeostasis. Here, we show that the NTD of C. vibroides PcoB is critical for PcoB function and stability, tolerating the swapping with the poorly conserved E. coli PcoB NTD and significant truncations. Unexpectedly, the predicted signal peptide was dispensable, challenging traditional concepts of protein translocation mechanisms. Moreover, the PcoB NTD plays a surprising role in stabilizing the periplasmic multicopper oxidase PcoA, encoded within the same operon as PcoB, highlighting a new role for a disordered region.

INSTRUMENT(S):

ORGANISM(S): Caulobacter Crescentus (strain Na1000 / Cb15n)

SUBMITTER: Marc Dieu  

LAB HEAD: Jean-Yves Matroule

PROVIDER: PXD067297 | Pride | 2025-09-05

REPOSITORIES: Pride