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

McLaughlin, Krystle J, Strain-Damerell, Claire M, Xie, Kefang, Brekasis, Dimitris, Soares, Alexei S, Paget, Mark and Kielkopf, Clara L (2010) Structural basis for NADH/NAD+ redox sensing by a Rex family repressor. Molecular Cell, 38 (4). pp. 563-575. ISSN 1097-2765

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science
Depositing User: Claire Strain-Damerell
Date Deposited: 06 Feb 2012 18:41
Last Modified: 10 Jul 2013 10:06
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