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

Abstract

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.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org.:
DOE - OFFICE OF SCIENCE
OSTI Identifier:
1014298
Report Number(s):
BNL-93654-2010-JA
Journal ID: ISSN 1097-2765; R&D Project: BO-070; KP1605010; TRN: US201111%%251
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Molecular Cell
Additional Journal Information:
Journal Volume: 38; Journal Issue: 4; Journal ID: ISSN 1097-2765
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ADENINES; AVAILABILITY; BACTERIA; CLOSURES; DNA; GENE REGULATION; GENES; MUTAGENESIS; NADP; NICOTINAMIDE; ORIENTATION; OXYGEN; RESIDUES; SENSORS

Citation Formats

McLaughlin, K.J., Soares, A., Strain-Damerell, C. M., Xie, K., Brekasis, D., Pagent, M. S. B., and Kielkopf, C. L. Structural Basis for NADH/NAD+ Redox Sensing by a Rex Family Repressor. United States: N. p., 2010. Web. doi:10.1016/j.molcel.2010.05.006.
McLaughlin, K.J., Soares, A., Strain-Damerell, C. M., Xie, K., Brekasis, D., Pagent, M. S. B., & Kielkopf, C. L. Structural Basis for NADH/NAD+ Redox Sensing by a Rex Family Repressor. United States. doi:10.1016/j.molcel.2010.05.006.
McLaughlin, K.J., Soares, A., Strain-Damerell, C. M., Xie, K., Brekasis, D., Pagent, M. S. B., and Kielkopf, C. L. Fri . "Structural Basis for NADH/NAD+ Redox Sensing by a Rex Family Repressor". United States. doi:10.1016/j.molcel.2010.05.006.
@article{osti_1014298,
title = {Structural Basis for NADH/NAD+ Redox Sensing by a Rex Family Repressor},
author = {McLaughlin, K.J. and Soares, A. and Strain-Damerell, C. M. and Xie, K. and Brekasis, D. and Pagent, M. S. B. and Kielkopf, C. L.},
abstractNote = {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.},
doi = {10.1016/j.molcel.2010.05.006},
journal = {Molecular Cell},
issn = {1097-2765},
number = 4,
volume = 38,
place = {United States},
year = {2010},
month = {5}
}