The flavodoxin FldA activates the class 1a ribonucleotide reductase of Campylobacter jejuni

Alqurashi, Abdulmajeed, Alfs, Laura, Swann, Jordan, Butt, Julea N. and Kelly, David J. (2021) The flavodoxin FldA activates the class 1a ribonucleotide reductase of Campylobacter jejuni. Molecular Microbiology, 116 (1). pp. 343-358. ISSN 0950-382X

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Abstract

Campylobacter jejuni is a microaerophilic zoonotic pathogen with an atypical respiratory Complex I that oxidizes a flavodoxin (FldA) instead of NADH. FldA is essential for viability and is reduced via pyruvate and 2-oxoglutarate oxidoreductases (POR/OOR). Here, we show that FldA can also be reduced by FqrB (Cj0559), an NADPH:FldA reductase. An fqrB deletion mutant was viable but displayed a significant growth defect. FqrB is related to flavoprotein reductases from Gram-positive bacteria that can reduce NrdI, a specialized flavodoxin that is needed for tyrosyl radical formation in NrdF, the beta subunit of class 1b-type (Mn) ribonucleotide reductase (RNR). However, C. jejuni possesses a single class Ia-type (Fe) RNR (NrdAB) that would be expected to be ferredoxin dependent. We show that CjFldA is an unusually high potential flavodoxin unrelated to NrdI, yet growth of the fqrB mutant, but not the wild-type or a complemented strain, was stimulated by low deoxyribonucleoside (dRNS) concentrations, suggesting FldA links FqrB and RNR activity. Using purified proteins, we confirmed the NrdB tyrosyl radical could be regenerated in an NADPH, FqrB, and FldA dependent manner, as evidenced by both optical and electron paramagnetic resonance (EPR) spectroscopy. Thus, FldA activates RNR in C. jejuni, partly explaining its essentiality.

Item Type: Article
Uncontrolled Keywords: cj0559,fqrb,flavin,flavodoxin reductase,tyrosyl radical,microbiology,molecular biology ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Science > School of Chemistry
Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 29 Mar 2021 23:56
Last Modified: 30 Sep 2021 16:18
URI: https://ueaeprints.uea.ac.uk/id/eprint/79576
DOI: 10.1111/mmi.14715

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