TY - JOUR
T1 - Structure and Function of an ADP-Ribose-Dependent Transcriptional Regulator of NAD Metabolism
AU - Huang, Nian
AU - De Ingeniis, Jessica
AU - Galeazzi, Luca
AU - Mancini, Chiara
AU - Korostelev, Yuri D.
AU - Rakhmaninova, Alexandra B.
AU - Gelfand, Mikhail S.
AU - Rodionov, Dmitry A.
AU - Raffaelli, Nadia
AU - Zhang, Hong
N1 - Funding Information:
The authors wish to thank Drs. Andrei Osterman, Giulio Magni, Nick Grishin, and Silverio Ruggieri for helpful discussion; Lisa Kinch for critical reading of the manuscript; Adolfo Amici for technical assistance; and Eric Allen Hill for providing the S. oneidensis cell volume information. This work was supported by a Welch Foundation grant (I-5015) and in part by a National Institutes of Health grant (AI059146). The work of D.A.R. was partially supported by the “Integrated Biology of Shewanella” grant (PI J. Fredrikson) from the U.S. Department of Energy, Office of Biological and Environmental Research under the Genomics:GTL Program. M.S.G., A.B.R., and Y.D.K. were partially supported by grants from the Howard Hughes Medical Institute (55005610) and the Molecular and Cellular Biology program of the Russian Academy of Sciences (to M.S.G.).
PY - 2009/7/15
Y1 - 2009/7/15
N2 - Besides its function as an essential redox cofactor, nicotinamide adenine dinucleotide (NAD) also serves as a consumable substrate for several reactions with broad impact on many cellular processes. NAD homeostasis appears to be tightly controlled, but the mechanism of its regulation is little understood. Here we demonstrate that a previously predicted bacterial transcriptional regulator, NrtR, represses the transcription of NAD biosynthetic genes in vitro. The NAD metabolite ADP-ribose functions as an activator suppressing NrtR repressor activity. The presence of high ADP-ribose levels in the cell is indicative of active NAD turnover in bacteria, which could signal the activation of NAD biosynthetic gene expression via inhibiting the repressor function of NrtR. By comparing the crystal structures of NrtR in complex with DNA and with ADP-ribose, we identified a "Nudix switch" element that likely plays a critical role in the allosteric regulation of DNA binding and repressor function of NrtR.
AB - Besides its function as an essential redox cofactor, nicotinamide adenine dinucleotide (NAD) also serves as a consumable substrate for several reactions with broad impact on many cellular processes. NAD homeostasis appears to be tightly controlled, but the mechanism of its regulation is little understood. Here we demonstrate that a previously predicted bacterial transcriptional regulator, NrtR, represses the transcription of NAD biosynthetic genes in vitro. The NAD metabolite ADP-ribose functions as an activator suppressing NrtR repressor activity. The presence of high ADP-ribose levels in the cell is indicative of active NAD turnover in bacteria, which could signal the activation of NAD biosynthetic gene expression via inhibiting the repressor function of NrtR. By comparing the crystal structures of NrtR in complex with DNA and with ADP-ribose, we identified a "Nudix switch" element that likely plays a critical role in the allosteric regulation of DNA binding and repressor function of NrtR.
KW - PROTEINS
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U2 - 10.1016/j.str.2009.05.012
DO - 10.1016/j.str.2009.05.012
M3 - Article
C2 - 19604474
AN - SCOPUS:67649986228
SN - 0969-2126
VL - 17
SP - 939
EP - 951
JO - Structure
JF - Structure
IS - 7
ER -