University of Sussex
Browse

File(s) not publicly available

Structural basis for NADH/NAD+ redox sensing by a Rex family repressor

journal contribution
posted on 2023-06-07, 20:59 authored by Krystle J McLaughlin, Claire M Strain-Damerell, Kefang Xie, Dimitris Brekasis, Alexei S Soares, Mark PagetMark Paget, Clara L Kielkopf
Nicotinamide adenine dinucleotides have emerged as key signals of the cellular redox state. Yet the structural basis for allosteric gene regulation by the ratio of reduced NADH to oxidized NAD+ is poorly understood. A key sensor among Gram-positive bacteria, Rex represses alternative respiratory gene expression until a limited oxygen supply elevates the intracellular NADH:NAD+ ratio. Here we investigate the molecular mechanism for NADH/NAD+ sensing among Rex family members by determining structures of Thermus aquaticus Rex bound to (1) NAD+, (2) DNA operator, and (3) without ligand. Comparison with the Rex/NADH complex reveals that NADH releases Rex from the DNA site following a 40° closure between the dimeric subunits. Complementary site-directed mutagenesis experiments implicate highly conserved residues in NAD-responsive DNA-binding activity. These rare views of a redox sensor in action establish a means for slight differences in the nicotinamide charge, pucker, and orientation to signal the redox state of the cell.

History

Publication status

  • Published

Journal

Molecular Cell

ISSN

1097-2765

Issue

4

Volume

38

Page range

563-575

Pages

13.0

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC