KÖRNER H, SOFIA HJ, ZUMFT WG
Phylogeny of the bacterial superfamily
of Crp-Fnr transcription regulators: exploiting the metabolic spectrum
by controlling alternative gene programs.
FEMS Microbiol Rev 27: 559-592 (2003)
The Crp-Fnr regulators, named after the first two identified members,
are DNA-binding proteins which predominantly function as positive
transcription factors, though roles of repressors are also important.
Among over 1200 proteins with an N-terminally located
nucleotide-binding domain similar to the cyclic adenosine monophosphate
(cAMP) receptor protein, the distinctive additional trait of the
Crp-Fnr superfamily is a C-terminally located helix-turn-helix motif
for DNA binding. From a curated database of 369 family members
exhibiting both features, we provide a protein tree of Crp-Fnr proteins
according to their phylogenetic relationships. This results in the
assembly of the regulators ArcR, CooA, CprK, Crp, Dnr, FixK, Flp, Fnr,
FnrN, MalR, NnrR, NtcA, PrfA, and YeiL and their homologs in distinct
clusters. Lead members and representatives of these groups are
described, placing emphasis on the less well-known regulators and
target processes. Several more groups consist of sequence-derived
proteins of unknown physiological role; some of them are tight clusters
of highly similar members. The Crp-Fnr regulators stand out in
responding to a broad spectrum of intracellular and exogenous signals
such as cAMP, anoxia, the redox state, oxidative and nitrosative
stress, nitric oxide, carbon monoxide, 2-oxoglutarate, or temperature.
To accomplish their roles Crp-Fnr members have intrinsic sensory
modules allowing the binding of allosteric effector molecules, or have
prosthetic groups for the interaction with the signal. The regulatory
adaptability and structural flexibility represented in the Crp-Fnr
scaffold has led to the evolution of an important group of
physiologically versatile transcription factors.