Structural Basis for NADH/NAD+ Redox Sensing by a Rex Family Repressor

Journal Article · Fri May 28 04:00:00 EDT 2010 · Molecular Cell

DOI:https://doi.org/10.1016/j.molcel.2010.05.006· OSTI ID:1014298

McLaughlin, K J; Soares, A; Strain-Damerell, C M; Xie, K; Brekasis, D; Pagent, M S. B.; Kielkopf, C L

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{sup +} 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{sup +} ratio. Here we investigate the molecular mechanism for NADH/NAD{sup +} sensing among Rex family members by determining structures of Thermus aquaticus Rex bound to (1) NAD{sup +}, (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{sup o} 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.

• Research Organization: BROOKHAVEN NATIONAL LABORATORY (BNL)
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1014298
• Report Number(s): BNL--93654-2010-JA; KP1605010
• Journal Information: Molecular Cell, Journal Name: Molecular Cell Journal Issue: 4 Vol. 38; ISSN 1097-2765
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ADENINES
AVAILABILITY
BACTERIA
CLOSURES
DNA
GENE REGULATION
GENES
MUTAGENESIS
NADP
NICOTINAMIDE
ORIENTATION
OXYGEN
RESIDUES
SENSORS