Catabolite Activator Protein
The CAP/FNR family of Proteins
CAP is one of several members of the CAP/FNR (or CRP/FNR) family of transcription factors, which are widely distributed throughout bacteria. There are around 200 protein members of this family currently in the InterPro database. The CAP/FNR family of proteins are not universal bacterial regulators, but are adapted to the needs of specific groups of bacteria, especially those living in fluctuating environments. Members of this family of regulators help to bring about metabolic diversity in the groups of bacteria that they are found in. Examples of the many ways CAP/FNR regulators take part in bacterial metabolism can be shown by the functions of other members of the family, which include: Fnr, an FeS protein that acts as an oxygen-responsive transcription regulator; FnrN, an FeS proteins involved in nitrogen fixation, photosynthesis and the degradation of aromatics; FixK, which is essential for fixing dinitrogen in a symbiotic environment; Flp, which acts as an oxidative stress sensor to mediate the stress response; YeiL, which functions during the stationary growth phase under aerobic conditions as part of a starvation survival response; Dnr, which helps maintain NO homeostasis under anaerobic conditions; NnrR, which is involved in the NO response to establish nitrite respiration; NtcA, which mediates nitrogen control in cyanobacteria; ArcR, which mediates the expression of the deiminase pathway, helping to extract energy from arginine catabolism; MalR, which regulates genes required for the utilisation of maltotriose; PrfA, which mediates the expression of pathogenicity factors from Listeria spp.; CrpK, which is involved in halorespiration; and CooA, which uses Haem as a prosthetic group to regulate the expression of genes required for CO-oxidative growth. Examples of each of these proteins came be found in the Table. The same mechanism of gene activation described for CAP can be applied to these different CAP homologues. The distinctive trait that defines members of the CAP/FNR family is the C-terminally located helix-turn-helix (HTH) motif, consisting of two helices joined by a turn that fits into the major groove of DNA. The N-terminal allosteric-binding domain of the CAP/FNR proteins is not unique to this family, but is shared by many proteins of varying functions in different kingdoms of life, including cAMP- and cGMP-dependent protein kinases (cAPK, cGPK), and vertebrate cyclic nucleotide-gated ion channels. CAP/FNR family protein members bind different types of cofactors. The regulatory adaptability and structural flexibility represented in the CAP/FNR protein scaffold has led to the evolution of an important group of physiologically versatile transcription factors.
P03020 Escherichia coli catabolite
activator protein entry from InterPro
|
InterPro Entry |
Method accession |
Graphical match |
Method name |
|
IPR000595 |
PF00027 |
|
cNMP_binding |
|
IPR000595 |
PS00888 |
|
CNMP_BINDING_1 |
|
IPR000595 |
PS00889 |
|
CNMP_BINDING_2 |
|
IPR000595 |
PS50042 |
|
CNMP_BINDING_3 |
|
IPR000595 |
SM00100 |
|
cNMP |
|
IPR001808 |
PF00325 |
|
crp |
|
IPR001808 |
PR00034 |
|
HTHCRP |
|
IPR001808 |
PS00042 |
|
HTH_CRP_FAMILY |
|
IPR001808 |
SM00419 |
|
HTH_CRP |
|
NONE |
1cgpA1 |
|
1cgpA1 |
|
NONE |
1cgpA2 |
|
1cgpA2 |
|
NONE |
d1cgpa1 |
|
d1cgpa1 |
|
NONE |
d1cgpa2 |
|
d1cgpa2 |
What InterPro tells us
From the graphical match above, you can see that the signatures in InterPro for the E. coli CAP protein are subdivided into two groups. These groups give you information about the domain architecture of the protein, as well as its family relationships.
InterPro entry IPR000595 represents the cyclic nucleotide-binding domain of CAP. As mentioned above, this domain is not unique to the CAP/FNR family of proteins, being found in several unrelated families. It does have a conserved eight-stranded beta-barrel structure, containing six invariant residues, three of which are glycines involved in maintaining the beta-barrel. IPR000595 has five signatures representing this domain: PF00027 from the PFAM database, SM00100 from the SMART database, and three signatures from the Prosite database, PS50042, PS00888 and PS00889, the latter two representing patterns from the regions between beta-barrels 2 and 3 (containing two conserved glycines), and beta-barrels 6 and 7 (containing a conserved glycine), respectively. The signatures in this InterPro entry identify about 800 protein matches from different families.
InterPro
entry IPR001808 represents the CAP (CRP)
family of regulatory proteins. The four
signatures in this entry are all from the C-terminal HTH domain, which is unique
to the CAP/FNR family. The IPR001808
signatures representing this family are:
PF00325
from the PFAM database, PR00034 from the PRINTS database, PS00042
from the Prosite database, and SM00419 from the SMART database, all of which include the
entire HTH motif in their methods. The
signatures in this InterPro entry identify about 200 protein matches from the
CAP/FNR family.
The
remaining four entries in the table above are from the structural
classification databases CATH and SCOP (the names such as d1cgpa2 are derived
from the PDB entry upon which they are based; here PDB entry 1cgp, chain a,
region 2). If you follow the links to
these databases you will find descriptions of the structural features and
classification of these domains, as well as links to the corresponding PDB entries: 1cgpA1 and d1cgpa2 for information on the structure of the N-terminal
domain; 1cgpA2 and d1cgpa1 for information on the structure of the C-terminal
domain.
What the structure tells us
The crystallographic structure of the catabolite activator protein has been determined. A description and visualisation of the structural features of CAP can be found at the PDB database. Here you can see the structural basis for the CAP transcriptional activation mechanism.