CooA

{{Short description|Heme-containing transcription factor}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox nonhuman protein | Name = Carbon monoxide oxidation system transcription regulator CooA | image = RRcOOA 1FT9.png | width = | caption = Crystallographic structure of the homodimeric RRcOOA (monomers colored cyan and green) bound to heme (spheres) | Organism = ''Rhodospirillum rubrum'' | TaxID = 1085 | Symbol = cooA | AltSymbols = | ATC_prefix = | ATC_suffix = | ATC_supplemental = | CAS_number = | CAS_supplemental = | DrugBank = | EntrezGene = | HomoloGene = | PDB = 1FT9 | RefSeqmRNA = | RefSeqProtein = | UniProt = P72322 | ECnumber = | Chromosome = | EntrezChromosome = | GenLoc_start = | GenLoc_end = }}

'''CooA''' is a heme-containing transcription factor that responds to the presence of carbon monoxide. This protein forms homodimers and is a homolog of cAMP receptor protein.<ref>{{cite journal | vauthors = Körner H, Sofia HJ, Zumft WG | title = Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs | journal = FEMS Microbiology Reviews | volume = 27 | issue = 5 | pages = 559–592 | date = December 2003 | pmid = 14638413 | doi = 10.1016/S0168-6445(03)00066-4 | doi-access = free }}</ref>

== Homologs ==

The most well-studied CooA homolog comes from ''Rhodospirillum rubrum'' (''Rr''CooA), but the homolog from ''Carboxydothermus hydrogenoformans'' (''Ch''CooA) has also been characterized.<ref>{{cite journal | vauthors = Shimizu T, Huang D, Yan F, Stranava M, Bartosova M, Fojtíková V, Martínková M | title = Gaseous O2, NO, and CO in signal transduction: structure and function relationships of heme-based gas sensors and heme-redox sensors | journal = Chemical Reviews | volume = 115 | issue = 13 | pages = 6491–6533 | date = July 2015 | pmid = 26021768 | doi = 10.1021/acs.chemrev.5b00018 }}</ref>

The main structural difference between these homologs lies in ferric heme coordination. In ''Rr''CooA, the ferric heme iron is ligated by a cysteine and the amine of the N-terminal proline; in the ferrous state, a ligand switch occurs in which a histidine replaces the thiolate.<ref>{{cite journal | vauthors = Shelver D, Thorsteinsson MV, Kerby RL, Chung SY, Roberts GP, Reynolds MF, Parks RB, Burstyn JN | title = Identification of two important heme site residues (cysteine 75 and histidine 77) in CooA, the CO-sensing transcription factor of Rhodospirillum rubrum | journal = Biochemistry | volume = 38 | issue = 9 | pages = 2669–2678 | date = March 1999 | pmid = 10052937 | doi = 10.1021/bi982658j }}</ref><ref>{{cite journal | vauthors = Dhawan IK, Shelver D, Thorsteinsson MV, Roberts GP, Johnson MK | title = Probing the heme axial ligation in the CO-sensing CooA protein with magnetic circular dichroism spectroscopy | journal = Biochemistry | volume = 38 | issue = 39 | pages = 12805–12813 | date = September 1999 | pmid = 10504250 | doi = 10.1021/bi991303c }}</ref><ref>{{cite journal | vauthors = Clark RW, Youn H, Parks RB, Cherney MM, Roberts GP, Burstyn JN | title = Investigation of the role of the N-terminal proline, the distal heme ligand in the CO sensor CooA | journal = Biochemistry | volume = 43 | issue = 44 | pages = 14149–14160 | date = November 2004 | pmid = 15518565 | doi = 10.1021/bi0487948 }}</ref> In contrast, ''Ch''CooA features histidine and the N-terminal amine as ligands in both ferric and ferrous states.<ref>{{cite journal | vauthors = Inagaki S, Masuda C, Akaishi T, Nakajima H, Yoshioka S, Ohta T, Pal B, Kitagawa T, Aono S | title = Spectroscopic and redox properties of a CooA homologue from Carboxydothermus hydrogenoformans | journal = The Journal of Biological Chemistry | volume = 280 | issue = 5 | pages = 3269–3274 | date = February 2005 | pmid = 15537640 | doi = 10.1074/jbc.m409884200 | doi-access = free }}</ref>

== Structure ==

CooA is a homodimeric, heme-containing transcription factor of the CAP/CRP family, with each monomer comprising an N-terminal heme-binding regulatory domain and a C-terminal helix-turn-helix motif that acts as a DNA-binding domain. The N-terminal domain coordinates a b-type heme whose axial ligands differ between species (for example, His-Pro versus His-His), and carbon monoxide (CO) binding to this heme triggers conformational changes that activate DNA binding. The two subunits associate through a coiled-coil-like interface, positioning the paired helix–turn–helix motifs to recognize target palindromic sequences in promoter DNA and thereby regulate genes involved in CO oxidation.<ref name = "Lanzilotta_2000" /><ref name = "Komori_2007" /><ref name="Shelver_1997">{{cite journal | vauthors = Shelver D, Kerby RL, He Y, Roberts GP | title = CooA, a CO-sensing transcription factor from Rhodospirillum rubrum, is a CO-binding heme protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 21 | pages = 11216–20 | date = October 1997 | pmid = 9326589 | doi = 10.1073/pnas.94.21.11216 | pmc = 23420 }}</ref>

Several structures of CooA have been solved, including:

* ''Rr''CooA in the ferrous state (1FT9),<ref name = "Lanzilotta_2000">{{cite journal | vauthors = Lanzilotta WN, Schuller DJ, Thorsteinsson MV, Kerby RL, Roberts GP, Poulos TL | title = Structure of the CO sensing transcription activator CooA | journal = Nature Structural Biology | volume = 7 | issue = 10 | pages = 876–880 | date = October 2000 | pmid = 11017196 | doi = 10.1038/82820 | s2cid = 26285016 }}</ref> * ''Ch''CooA in the ferrous, imidazole-bound state (2FMY),<ref name = "Komori_2007">{{cite journal | vauthors = Komori H, Inagaki S, Yoshioka S, Aono S, Higuchi Y | title = Crystal structure of CO-sensing transcription activator CooA bound to exogenous ligand imidazole | journal = Journal of Molecular Biology | volume = 367 | issue = 3 | pages = 864–871 | date = March 2007 | pmid = 17292914 | doi = 10.1016/j.jmb.2007.01.043 }}</ref> * ''Ch''CooA in the ferrous, CO-bound state (2HKX).<ref>{{cite journal | vauthors = Borjigin M, Li H, Lanz ND, Kerby RL, Roberts GP, Poulos TL | title = Structure-based hypothesis on the activation of the CO-sensing transcription factor CooA | journal = Acta Crystallographica. Section D, Biological Crystallography | volume = 63 | issue = Pt 3 | pages = 282–287 | date = March 2007 | pmid = 17327664 | doi = 10.1107/S0907444906051638 | bibcode = 2007AcCrD..63..282B }}</ref>

==Function==

CooA responds to the presence of carbon monoxide and regulates the expression of carbon monoxide dehydrogenase, the enzyme that catalyzes the oxidation of CO to CO₂.

For both ''Rr''CooA and ''Ch''CooA, CO displaces the amine ligand at the heme and activates the protein, enabling DNA binding at the target promoter sequence.<ref>{{cite journal | vauthors = Roberts GP, Kerby RL, Youn H, Conrad M | title = CooA, a paradigm for gas sensing regulatory proteins | journal = Journal of Inorganic Biochemistry | volume = 99 | issue = 1 | pages = 280–292 | date = January 2005 | pmid = 15598507 | doi = 10.1016/j.jinorgbio.2004.10.032 }}</ref><ref>{{cite journal | vauthors = Aono S | title = Biochemical and biophysical properties of the CO-sensing transcriptional activator CooA | journal = Accounts of Chemical Research | volume = 36 | issue = 11 | pages = 825–831 | date = November 2003 | pmid = 14622029 | doi = 10.1021/ar020097p }}</ref>

== References == {{Reflist}}

{{Transcription factors}}

{{DEFAULTSORT:Transcription Factor}} Category:Gene expression Category:Protein families Category:Transcription factors Category:DNA Category:Gaseous signaling molecules