8T4C

Membrane-associated thioredoxin oxidoreductase FetE from Campylobacter jejuni

Summary for 8T4C

• Entry DOI: 10.2210/pdb8t4c/pdb
• Descriptor: Thioredoxin oxidoreductase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: fet system, iron uptake, disulfide reductase, oxidoreductase
• Biological source: Campylobacter jejuni subsp. jejuni
• Total number of polymer chains: 2
• Total formula weight: 32903.80

Authors

Chan, A.C.,Murphy, M.E. (deposition date: 2023-06-09, release date: 2023-08-09, Last modification date: 2024-05-22)

Primary citation

Richardson-Sanchez, T.,Chan, A.C.K.,Sabatino, B.,Lin, H.,Gaynor, E.C.,Murphy, M.E.P.
Dissecting components of the Campylobacter jejuni fetMP-fetABCDEF gene cluster in iron scavenging.
Biorxiv, 2023

PubMed Abstract: is a leading cause of bacterial gastroenteritis worldwide. Acute infection can be antecedent to highly debilitating long-term sequelae. Expression of iron acquisition systems is vital for to survive the low iron availability within the human gut. The gene cluster is known to be upregulated during human infection and under iron limitation. While FetM and FetP have been functionally linked to iron transport in prior work, here we assess the contribution by each of the downstream genes ( ) to growth during both iron-depleted and iron-replete conditions. Significant growth impairment was observed upon disruption of , , and , suggesting a role in iron acquisition for each encoded protein. FetA expression was modulated by iron-availability but not dependent on the presence of FetB, FetC, FetD, FetE or FetF. Functions of the putative thioredoxins FetE and FetF were redundant in iron scavenging, requiring a double deletion (Δ ) to exhibit a growth defect. FetE was expressed and the structure solved to 1.50 Å, revealing structural similarity to thiol-disulfide oxidases. Functional characterization in biochemical assays showed that FetE reduced insulin at a slower rate than Trx and that together, FetEF promoted substrate oxidation in cell extracts, suggesting that FetE (and presumably FetF) are oxidoreductases that can mediate oxidation . This study advances our understanding of the contributions by the gene cluster to virulence at a genetic and functional level, providing foundational knowledge towards mitigating -related morbidity and mortality.

PubMed: 37461706
DOI: 10.1101/2023.07.05.547857

Experimental method

X-RAY DIFFRACTION (1.5 Å)