The asnC-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of
about 60 amino acids present in transcription regulators of the asnC/lrp
family. This family of prokaryotic regulators is named after Escherichia coli
asnC and Leucine-responsive Regulatory Protein (lrp), which are a regulator of
asparagine synthesis and a global regulator of various operons, respectively
. AsnC/lrp-like proteins are present in bacteria and archaea . The
DNA-binding asnC-type HTH domain occurs usually in the N-terminal part. The
C-terminal part can contain an effector-binding domain and/or an
oligomerization domain. Regulators of the asnC/lrp family can be dimers,
tetramers, octamers and hexadecamers [3,4]. These proteins regulate amino acid
metabolism and related processes. Lrp is a global regulator of E. coli,
involved in amino acid metabolism and pili synthesis by affecting
transcription of at least 10% of its genes. Most lrp homologues appear to be
specific regulators of amino acid metabolism . Various amino acids act as
specific effectors and can either activate or repress transcription of
metabolic enzymes. Many asnC/lrp-like proteins can also repress their own
The crystal structure of hyperthermophilic archaeal lrpA shows that the
N-terminal, DNA binding domain contains a core of three α-helices,
followed by a single β-strand, which connects as a flexible hinge to the
effector binding domain (see <PDB:1I1G>). The second and third helices,
connected via a turn, comprise the helix-turn-helix motif. Helix 3 is termed
the recognition helix as it binds the DNA major groove, like in other HTHs.
Most E. coli lrp DNA binding mutants are positioned in the lrpA structure on
the HTH and three are on the hinge .
Some proteins known to contain an asnC-type HTH domain:
- Escherichia coli Leucine-responsive Regulatory Protein (lrp), a global
transcriptional regulator of 35-75 different genes involved in amino acid
biosynthesis, amino acid degradation, transport or pili formation. Binding
of leucine by lrp can stimulate or reduce the regulatory effect of
activation for some operons or repression for others. Lrp negatively
autoregulates the lrp gene, independently of leucine.
- Salmonella typhimurium lrp, a global leucine-responsive regulator involved
in branched-chain amino acid biosynthesis, pili formation and plasmid
- Escherichia coli asnC, a specific asparagine-dependent transcriptional
activator of asparagine biosynthesis. AsnC is also an asparagine-
independent repressor of its own transcription.
- Pseudomonas putida bkdR, a specific autoregulatory transcriptional
regulator, involved in catabolism of branched-chain amino acids.
- Agrobacterium tumefaciens putR, a specific proline-responsive regulator of
- Bacillus subtilis lrpA/lrpB and lrpC, transcriptional regulators involved
in serine-glycine interconversion, sporulation and amino acid metabolism.
LrpC binds to a specific DNA structure and wraps and overwinds the DNA .
- Bacillus subtilis azlB, a specific transcriptional repressor of branched-
chain amino acid transport.
- Pyrococcus furiosus lrpA, a putative lrp with negative autoregulation.
- Zymomonas mobilis grp, a repressor of the glutamate uptake operon.
The pattern we use to detect these proteins spans the complete
helix-turn-helix motif and extends one residue downstream and one upstream of
the HTH extremities. The profile we developed covers the entire asnC-type DNA
binding domain, from the first helix to the end of the hinge.
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