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261  structures 7257  species 0  interactions 31425  sequences 1023  architectures

Family: Fer4 (PF00037)

Summary: 4Fe-4S binding domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Ferredoxin". More...

Ferredoxin Edit Wikipedia article

Ferredoxins (from Latin ferrum: iron + redox, often abbreviated "fd") are iron–sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co. and applied to the "iron protein" first purified in 1962 by Mortenson, Valentine, and Carnahan from the anaerobic bacterium Clostridium pasteurianum.[1][2]

Another redox protein, isolated from spinach chloroplasts, was termed "chloroplast ferredoxin".[3] The chloroplast ferredoxin is involved in both cyclic and non-cyclic photophosphorylation reactions of photosynthesis. In non-cyclic photophosphorylation, ferredoxin is the last electron acceptor thus reducing the enzyme NADP+ reductase. It accepts electrons produced from sunlight-excited chlorophyll and transfers them to the enzyme ferredoxin: NADP+ oxidoreductase EC 1.18.1.2.

Ferredoxins are small proteins containing iron and sulfur atoms organized as iron–sulfur clusters. These biological "capacitors" can accept or discharge electrons, with the effect of a change in the oxidation state of the iron atoms between +2 and +3. In this way, ferredoxin acts as an electron transfer agent in biological redox reactions.

Other bioinorganic electron transport systems include rubredoxins, cytochromes, blue copper proteins, and the structurally related Rieske proteins.

Ferredoxins can be classified according to the nature of their iron–sulfur clusters and by sequence similarity.

Bioenergetics of ferredoxins

Ferredoxins typically carry out a single electron transfer.

Fd0
ox
+  e− Fd−
red

However a few bacterial ferredoxins (of the 2[4Fe4S] type) have two iron sulfur clusters and can carry out two electron transfer reactions. Depending on the sequence of the protein, the two transfers can have nearly identical reduction potentials or they may be significantly different.[4][5]

Fd0
ox
+  e− Fd−
red

Fd−
red
+  e− Fd2−
red

Ferredoxins are one of the most reducing biological electron carriers. They typically have a mid point potential of -420 mV.[6] The reduction potential of a substance in the cell will differ from its midpoint potential depending on the concentrations of its reduced and oxidized forms. For a one electron reaction, the potential changes by around 60 mV for each power of ten change in the ratio of the concentration. For example, if the ferredoxin pool is around 95% reduced, the reduction potential will be around -500 mV.[7] In comparison, other biological reactions mostly have less reducing potentials: for example the primary biosynthetic reductant of the cell, NADPH has a cellular redox potential of -370 mV (E
0
= -320 mV).

Depending on the sequence of the supporting protein ferredoxins have reduction potential from around -500mv[6][8] to -340 mV.[9] A single cell can have multiple types of ferredoxins where each type is tuned to optimally carry out different reactions.[10]

Reduction of ferredoxin

The highly reducing ferredoxins are reduced either by using another strong reducing agent, or by using some source of energy to "boost" electrons from less reducing sources to the ferredoxin.[11]

Direct reduction

Reactions that reduce Fd include the oxidation of aldehydes to acids like the glyceraldehyde to glycerate reaction (-580 mV), the carbon monoxide dehydrogenase reaction (-520 mV), and the 2-oxoacid:Fd Oxidoreductase reactions (-500 mV)[12][8] like the reaction carried out by pyruvate synthase.[7]

Membrane potential coupled reduction

Ferredoxin can also be reduced by using NADH (-320 mV) or H
2
(-414 mV), but these processes are coupled to the consumption of the membrane potential to power the "boosting" of electrons to the higher energy state.[6] The Rnf complex is a widespread membrane protein in bacteria that reversibly transfers electrons between NADH and ferredoxin while pumping Na+
or H+
ions across the membrane. The chemiosmotic potential of the membrane is consumed to power the unfavorable reduction of Fd
ox
by NADH. This reaction is an essential source of Fd−
red
in many autotrophic organisms. If the cell is growing on substrates that provide excess Fd−
red
, the Rnf complex can transfer these electrons to NAD+
and store the resultant energy in the membrane potential.[13] The energy converting hydrogenases (Ech) are a family of enzymes that reversibly couple the transfer of electrons between Fd and H
2
while pumping H +
ions across the membrane to balance the energy difference. [14]

Fd0
ox
+ NADH + Na+
outside
Fd2−
red
+ NAD+
+ Na+
inside

Fd0
ox
+ H
2
+ H+
outside
Fd2−
red
+ H+
+ H+
inside

Electron bifurcation

The unfavourable reduction of Fd from a less reducing electron donor can be coupled simultaneously with the favourable reduction of an oxidising agent through an electron bifurcation reaction.[6] An example of the electron bifurcation reaction is the generation of Fd−
red
for nitrogen fixation in certain aerobic diazotrophs. Typically in oxidative phosphorylation the transfer of electrons from NADH to Ubiquinone(Q) is coupled to charging the proton motive force. In Azotobacter the energy released by transferring one electron from NADH to Q is used to simultaneously boost the transfer of one electron from NADH to Fd.[15][16]

Direct reduction of high potential ferredoxins

Some ferredoxins have a sufficiently high redox potential that they can be directly reduced by NADPH. One such ferredoxin is adrenoxin (-274mV) which takes part in the biosynthesis of many mammalian steroids.[17] The ferredoxin Fd3 in the roots of plants that reduces nitrate and sulfite has a midpoint potential of -337mV and is also reduced by NADPH.[10]

Fe2S2 ferredoxins

2Fe-2S iron-sulfur cluster binding domain
Fe2S2.svg
Structural representation of an Fe2S2 ferredoxin.
Identifiers
SymbolFer2
PfamPF00111
Pfam clanCL0486
InterProIPR001041
PROSITEPDOC00642
SCOP23fxc / SCOPe / SUPFAM
OPM protein1kf6

Members of the 2Fe–2S ferredoxin superfamily (InterPro: IPR036010) have a general core structure consisting of beta(2)-alpha-beta(2), which includes putidaredoxin, terpredoxin, and adrenodoxin.[18][19][20][21] They are proteins of around one hundred amino acids with four conserved cysteine residues to which the 2Fe–2S cluster is ligated. This conserved region is also found as a domain in various metabolic enzymes and in multidomain proteins, such as aldehyde oxidoreductase (N-terminal), xanthine oxidase (N-terminal), phthalate dioxygenase reductase (C-terminal), succinate dehydrogenase iron–sulphur protein (N-terminal), and methane monooxygenase reductase (N-terminal).

Plant-type ferredoxins

One group of ferredoxins, originally found in chloroplast membranes, has been termed "chloroplast-type" or "plant-type" (InterPro: IPR010241). Its active center is a [Fe2S2] cluster, where the iron atoms are tetrahedrally coordinated both by inorganic sulfur atoms and by sulfurs of four conserved cysteine (Cys) residues.

In chloroplasts, Fe2S2 ferredoxins function as electron carriers in the photosynthetic electron transport chain and as electron donors to various cellular proteins, such as glutamate synthase, nitrite reductase, sulfite reductase, and the cyclase of chlorophyll biosynthesis.[22] Since the cyclase is a ferredoxin dependent enzyme this may provide a mechanism for coordination between photosynthesis and the chloroplasts need for chlorophyll by linking chlorophyll biosynthesis to the photosynthetic electron transport chain. In hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between reductase flavoproteins and oxygenase.

Thioredoxin-like ferredoxins

The Fe2S2 ferredoxin from Clostridium pasteurianum (Cp2FeFd; P07324) has been recognized as distinct protein family on the basis of its amino acid sequence, spectroscopic properties of its iron–sulfur cluster and the unique ligand swapping ability of two cysteine ligands to the [Fe2S2] cluster. Although the physiological role of this ferredoxin remains unclear, a strong and specific interaction of Cp2FeFd with the molybdenum-iron protein of nitrogenase has been revealed. Homologous ferredoxins from Azotobacter vinelandii (Av2FeFdI; P82802) and Aquifex aeolicus (AaFd; O66511) have been characterized. The crystal structure of AaFd has been solved. AaFd exists as a dimer. The structure of AaFd monomer is different from other Fe2S2 ferredoxins. The fold belongs to the α+β class, with first four β-strands and two α-helices adopting a variant of the thioredoxin fold.[23] UniProt categorizes these as the "2Fe2S Shethna-type ferredoxin" family.[24]

Adrenodoxin-type ferredoxins

ferredoxin 1
3P1M.pdb1.png
Crystal structure of human ferredoxin-1 (FDX1).[25]
Identifiers
SymbolFDX1
Alt. symbolsFDX
NCBI gene2230
HGNC3638
OMIM103260
RefSeqNM_004109
UniProtP10109
Other data
LocusChr. 11 q22.3

Adrenodoxin (adrenal ferredoxin; InterPro: IPR001055), putidaredoxin, and terpredoxin make up a family of soluble Fe2S2 proteins that act as single electron carriers, mainly found in eukaryotic mitochondria and Proteobacteria. The human variant of adrenodoxin is referred to as ferredoxin-1 and ferredoxin-2. In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from NADPH:adrenodoxin reductase to membrane-bound cytochrome P450. In bacteria, putidaredoxin and terpredoxin transfer electrons between corresponding NADH-dependent ferredoxin reductases and soluble P450s.[26][27] The exact functions of other members of this family are not known, although Escherichia coli Fdx is shown to be involved in biogenesis of Fe–S clusters.[28] Despite low sequence similarity between adrenodoxin-type and plant-type ferredoxins, the two classes have a similar folding topology.

Ferredoxin-1 in humans participates in the synthesis of thyroid hormones. It also transfers electrons from adrenodoxin reductase to CYP11A1, a CYP450 enzyme responsible for cholesterol side chain cleavage. FDX-1 has the capability to bind to metals and proteins.[29] Ferredoxin-2 participates in heme A and iron–sulphur protein synthesis.[30]

Fe4S4 and Fe3S4 ferredoxins

The [Fe4S4] ferredoxins may be further subdivided into low-potential (bacterial-type) and high-potential (HiPIP) ferredoxins.

Low- and high-potential ferredoxins are related by the following redox scheme:

FdRedox.png

The formal oxidation numbers of the iron ions can be [2Fe3+, 2Fe2+] or [1Fe3+, 3Fe2+] in low-potential ferredoxins. The oxidation numbers of the iron ions in high-potential ferredoxins can be [3Fe3+, 1Fe2+] or [2Fe3+, 2Fe2+].

Bacterial-type ferredoxins

3Fe-4S binding domain
Fe3S4.png
Structural representation of an Fe3S4 ferredoxin.
Identifiers
SymbolFer4
PfamPF00037
InterProIPR001450
PROSITEPDOC00176
SCOP25fd1 / SCOPe / SUPFAM
OPM protein1kqf

A group of Fe4S4 ferredoxins, originally found in bacteria, has been termed "bacterial-type". Bacterial-type ferredoxins may in turn be subdivided into further groups, based on their sequence properties. Most contain at least one conserved domain, including four cysteine residues that bind to a [Fe4S4] cluster. In Pyrococcus furiosus Fe4S4 ferredoxin, one of the conserved Cys residues is substituted with aspartic acid.

During the evolution of bacterial-type ferredoxins, intrasequence gene duplication, transposition and fusion events occurred, resulting in the appearance of proteins with multiple iron–sulfur centers. In some bacterial ferredoxins, one of the duplicated domains has lost one or more of the four conserved Cys residues. These domains have either lost their iron–sulfur binding property or bind to a [Fe3S4] cluster instead of a [Fe4S4] cluster[31] and dicluster-type.[32]

3-D structures are known for a number of monocluster and dicluster bacterial-type ferredoxins. The fold belongs to the α+β class, with 2-7 α-helices and four β-strands forming a barrel-like structure, and an extruded loop containing three "proximal" Cys ligands of the iron–sulfur cluster.

High-potential iron–sulfur proteins

High potential iron–sulfur proteins (HiPIPs) form a unique family of Fe4S4 ferredoxins that function in anaerobic electron transport chains. Some HiPIPs have a redox potential higher than any other known iron–sulfur protein (e.g., HiPIP from Rhodopila globiformis has a redox potential of ca. 450 mV). Several HiPIPs have so far been characterized structurally, their folds belonging to the α+β class. As in other bacterial ferredoxins, the [Fe4S4] unit forms a cubane-type cluster and is ligated to the protein via four Cys residues.

Human proteins from ferredoxin family

Evolution of ferredoxins

References

  1. ^ Mortenson LE, Valentine RC, Carnahan JE (June 1962). "An electron transport factor from Clostridium pasteurianum". Biochemical and Biophysical Research Communications. 7 (6): 448–52. doi:10.1016/0006-291X(62)90333-9. PMID 14476372.
  2. ^ Valentine RC (December 1964). "Bacterial Ferredoxin". Bacteriological Reviews. 28 (4): 497–517. doi:10.1128/MMBR.28.4.497-517.1964. PMC 441251. PMID 14244728.
  3. ^ Tagawa K, Arnon DI (August 1962). "Ferredoxins as electron carriers in photosynthesis and in the biological production and consumption of hydrogen gas". Nature. 195 (4841): 537–43. Bibcode:1962Natur.195..537T. doi:10.1038/195537a0. PMID 14039612. S2CID 4213017.
  4. ^ Maiocco SJ, Arcinas AJ, Booker SJ, Elliott SJ (January 2019). "Parsing redox potentials of five ferredoxins found within Thermotoga maritima". Protein Science. 28 (1): 257–266. doi:10.1002/pro.3547. PMC 6295886. PMID 30418685.
  5. ^ Gao-Sheridan HS, Pershad HR, Armstrong FA, Burgess BK (March 1998). "Discovery of a novel ferredoxin from Azotobacter vinelandii containing two [4Fe-4S] clusters with widely differing and very negative reduction potentials". The Journal of Biological Chemistry. 273 (10): 5514–9. doi:10.1074/jbc.273.10.5514. PMID 9488675.
  6. ^ a b c d Buckel W, Thauer RK (2018). "Flavin-Based Electron Bifurcation, Ferredoxin, Flavodoxin, and Anaerobic Respiration With Protons (Ech) or NAD+ (Rnf) as Electron Acceptors: A Historical Review". Frontiers in Microbiology. 9: 401. doi:10.3389/fmicb.2018.00401. PMC 5861303. PMID 29593673.
  7. ^ a b Huwiler SG, Löffler C, Anselmann SE, Stärk HJ, von Bergen M, Flechsler J, et al. (February 2019). "One-megadalton metalloenzyme complex in Geobacter metallireducens involved in benzene ring reduction beyond the biological redox window". Proceedings of the National Academy of Sciences of the United States of America. 116 (6): 2259–2264. doi:10.1073/pnas.1819636116. PMC 6369795. PMID 30674680.
  8. ^ a b Li B, Elliott SJ (2016). "The Catalytic Bias of 2-Oxoacid:ferredoxin Oxidoreductase in CO2: Evolution and reduction through a ferredoxin-mediated electrocatalytic assay". Electrochimica Acta. 199: 349–356. doi:10.1016/j.electacta.2016.02.119.
  9. ^ Thamer W, Cirpus I, Hans M, Pierik AJ, Selmer T, Bill E, et al. (March 2003). "A two [4Fe-4S]-cluster-containing ferredoxin as an alternative electron donor for 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans". Archives of Microbiology. 179 (3): 197–204. doi:10.1007/s00203-003-0517-8. PMID 12610725. S2CID 23621034.
  10. ^ a b Hanke GT, Kimata-Ariga Y, Taniguchi I, Hase T (January 2004). "A post genomic characterization of Arabidopsis ferredoxins". Plant Physiology. 134 (1): 255–64. doi:10.1104/pp.103.032755. PMC 316305. PMID 14684843.
  11. ^ Boyd ES, Amenabar MJ, Poudel S, Templeton AS (February 2020). "Bioenergetic constraints on the origin of autotrophic metabolism". Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences. 378 (2165): 20190151. Bibcode:2020RSPTA.37890151B. doi:10.1098/rsta.2019.0151. PMC 7015307. PMID 31902344.
  12. ^ Gibson MI, Chen PY, Drennan CL (December 2016). "A structural phylogeny for understanding 2-oxoacid oxidoreductase function". Current Opinion in Structural Biology. 41: 54–61. doi:10.1016/j.sbi.2016.05.011. PMC 5381805. PMID 27315560.
  13. ^ Westphal L, Wiechmann A, Baker J, Minton NP, Müller V (November 2018). "The Rnf Complex Is an Energy-Coupled Transhydrogenase Essential To Reversibly Link Cellular NADH and Ferredoxin Pools in the Acetogen Acetobacterium woodii". Journal of Bacteriology. 200 (21). doi:10.1128/JB.00357-18. PMC 6182241. PMID 30126940.
  14. ^ Schoelmerich MC, Müller V (April 2020). "Energy-converting hydrogenases: the link between H2 metabolism and energy conservation". Cellular and Molecular Life Sciences. 77 (8): 1461–1481. doi:10.1007/s00018-019-03329-5. PMID 31630229. S2CID 204786346.
  15. ^ Ledbetter RN, Garcia Costas AM, Lubner CE, Mulder DW, Tokmina-Lukaszewska M, Artz JH, et al. (August 2017). "The Electron Bifurcating FixABCX Protein Complex from Azotobacter vinelandii: Generation of Low-Potential Reducing Equivalents for Nitrogenase Catalysis". Biochemistry. 56 (32): 4177–4190. doi:10.1021/acs.biochem.7b00389. PMC 7610252. PMID 28704608.
  16. ^ Poudel S, Colman DR, Fixen KR, Ledbetter RN, Zheng Y, Pence N, et al. (May 2018). "Electron Transfer to Nitrogenase in Different Genomic and Metabolic Backgrounds". Journal of Bacteriology. 200 (10). doi:10.1128/JB.00757-17. PMC 5915786. PMID 29483165.
  17. ^ Ewen KM, Ringle M, Bernhardt R (June 2012). "Adrenodoxin--a versatile ferredoxin". IUBMB Life. 64 (6): 506–12. doi:10.1002/iub.1029. PMID 22556163.
  18. ^ Armengaud J, Sainz G, Jouanneau Y, Sieker LC (February 2001). "Crystallization and preliminary X-ray diffraction analysis of a [2Fe-2S] ferredoxin (FdVI) from Rhodobacter capsulatus". Acta Crystallographica. Section D, Biological Crystallography. 57 (Pt 2): 301–3. doi:10.1107/S0907444900017832. PMID 11173487.
  19. ^ Sevrioukova IF (April 2005). "Redox-dependent structural reorganization in putidaredoxin, a vertebrate-type [2Fe-2S] ferredoxin from Pseudomonas putida". Journal of Molecular Biology. 347 (3): 607–21. doi:10.1016/j.jmb.2005.01.047. PMID 15755454.
  20. ^ Mo H, Pochapsky SS, Pochapsky TC (April 1999). "A model for the solution structure of oxidized terpredoxin, a Fe2S2 ferredoxin from Pseudomonas". Biochemistry. 38 (17): 5666–75. CiteSeerX 10.1.1.34.4745. doi:10.1021/bi983063r. PMID 10220356.
  21. ^ Beilke D, Weiss R, Löhr F, Pristovsek P, Hannemann F, Bernhardt R, Rüterjans H (June 2002). "A new electron transport mechanism in mitochondrial steroid hydroxylase systems based on structural changes upon the reduction of adrenodoxin". Biochemistry. 41 (25): 7969–78. doi:10.1021/bi0160361. PMID 12069587.
  22. ^ Stuart D, Sandström M, Youssef HM, Zakhrabekova S, Jensen PE, Bollivar DW, Hansson M (September 2020). "Aerobic Barley Mg-protoporphyrin IX Monomethyl Ester Cyclase is Powered by Electrons from Ferredoxin". Plants. 9 (9): 1157. doi:10.3390/plants9091157. PMC 7570240. PMID 32911631.
  23. ^ Yeh AP, Ambroggio XI, Andrade SL, Einsle O, Chatelet C, Meyer J, Rees DC (September 2002). "High resolution crystal structures of the wild type and Cys-55-->Ser and Cys-59-->Ser variants of the thioredoxin-like [2Fe-2S] ferredoxin from Aquifex aeolicus". The Journal of Biological Chemistry. 277 (37): 34499–507. doi:10.1074/jbc.M205096200. PMID 12089152.
  24. ^ family:"2fe2s shethna type ferredoxin family"
  25. ^ PDB: 3P1M​; Chaikuad A, Johansson, C, Krojer, T, Yue, WW, Phillips, C, Bray, JE, Pike, ACW, Muniz, JRC, Vollmar, M, Weigelt, J, Arrowsmith, CH, Edwards, AM, Bountra, C, Kavanagh, K, Oppermann, U (2010). "Crystal structure of human ferredoxin-1 (FDX1) in complex with iron-sulfur cluster". To be Published. doi:10.2210/pdb3p1m/pdb.
  26. ^ Peterson JA, Lorence MC, Amarneh B (April 1990). "Putidaredoxin reductase and putidaredoxin. Cloning, sequence determination, and heterologous expression of the proteins". The Journal of Biological Chemistry. 265 (11): 6066–73. doi:10.1016/S0021-9258(19)39292-0. PMID 2180940.
  27. ^ Peterson JA, Lu JY, Geisselsoder J, Graham-Lorence S, Carmona C, Witney F, Lorence MC (July 1992). "Cytochrome P-450terp. Isolation and purification of the protein and cloning and sequencing of its operon". The Journal of Biological Chemistry. 267 (20): 14193–203. doi:10.1016/S0021-9258(19)49697-X. PMID 1629218.
  28. ^ Tokumoto U, Takahashi Y (July 2001). "Genetic analysis of the isc operon in Escherichia coli involved in the biogenesis of cellular iron-sulfur proteins". Journal of Biochemistry. 130 (1): 63–71. doi:10.1093/oxfordjournals.jbchem.a002963. PMID 11432781.
  29. ^ "Entrez Gene: FDX1 ferredoxin 1".
  30. ^ "FDX2 ferredoxin 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 8 April 2019.
  31. ^ Fukuyama K, Matsubara H, Tsukihara T, Katsube Y (November 1989). "Structure of [4Fe-4S] ferredoxin from Bacillus thermoproteolyticus refined at 2.3 A resolution. Structural comparisons of bacterial ferredoxins". Journal of Molecular Biology. 210 (2): 383–98. doi:10.1016/0022-2836(89)90338-0. PMID 2600971.
  32. ^ Duée ED, Fanchon E, Vicat J, Sieker LC, Meyer J, Moulis JM (November 1994). "Refined crystal structure of the 2[4Fe-4S] ferredoxin from Clostridium acidurici at 1.84 A resolution". Journal of Molecular Biology. 243 (4): 683–95. doi:10.1016/0022-2836(94)90041-8. PMID 7966291.

Further reading

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

4Fe-4S binding domain Provide feedback

Superfamily includes proteins containing domains which bind to iron-sulfur clusters. Members include bacterial ferredoxins, various dehydrogenases, and various reductases. Structure of the domain is an alpha-antiparallel beta sandwich.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR017896

Ferredoxins are a group of iron-sulphur proteins which mediate electron transfer in a wide variety of metabolic reactions. Ferredoxins can be divided into several subgroups depending upon the physiological nature of the iron-sulphur cluster(s). One of these subgroups are the 4Fe-4S ferredoxins, which are found in bacteria and which are thus often referred as 'bacterial-type' ferredoxins. The structure of these proteins [ PUBMED:3129571 ] consists of the duplication of a domain of twenty six amino acid residues; each of these domains contains four cysteine residues that bind to a 4Fe-4S centre.

Several structures of the 4Fe-4S ferredoxin domain have been determined [ PUBMED:7966291 ]. The clusters consist of two interleaved 4Fe- and 4S-tetrahedra forming a cubane-like structure, in such a way that the four iron occupy the eight corners of a distorted cube. Each 4Fe-4S is attached to the polypeptide chain by four covalent Fe-S bonds involving cysteine residues.

A number of proteins have been found [ PUBMED:2185975 ] that include one or more 4Fe-4S binding domains similar to those of bacterial-type ferredoxins.

The pattern of cysteine residues in the iron-sulphur region is sufficient to detect this class of 4Fe-4S binding proteins. This entry represents the whole domain.

Note:In some bacterial ferredoxins, one of the two duplicated domains has lost one or more of the four conserved cysteines. The consequence of such variations is that these domains have either lost their iron-sulphur binding property or bind to a 3Fe-3S centre instead of a 4Fe-4S centre.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan 4Fe-4S (CL0344), which has the following description:

Superfamily includes proteins containing domains which bind to iron-sulfur clusters. Members include bacterial ferredoxins, various dehydrogenases and various reductases. The structure of the domain is an alpha-antiparallel beta sandwich.

The clan contains the following 29 members:

ETF_QO Fer4 Fer4_10 Fer4_11 Fer4_12 Fer4_13 Fer4_14 Fer4_15 Fer4_16 Fer4_17 Fer4_18 Fer4_19 Fer4_2 Fer4_20 Fer4_21 Fer4_22 Fer4_23 Fer4_24 Fer4_3 Fer4_4 Fer4_5 Fer4_6 Fer4_7 Fer4_8 Fer4_9 FeS Molybdop_Fe4S4 Nitr_red_alph_N RLI

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(528)
Full
(31425)
Representative proteomes UniProt
(152506)
RP15
(6012)
RP35
(17591)
RP55
(30736)
RP75
(48694)
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Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(528)
Full
(31425)
Representative proteomes UniProt
(152506)
RP15
(6012)
RP35
(17591)
RP55
(30736)
RP75
(48694)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(528)
Full
(31425)
Representative proteomes UniProt
(152506)
RP15
(6012)
RP35
(17591)
RP55
(30736)
RP75
(48694)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: fer4;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Eddy SR
Number in seed: 528
Number in full: 31425
Average length of the domain: 23.40 aa
Average identity of full alignment: 39 %
Average coverage of the sequence by the domain: 8.04 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 24
Family (HMM) version: 30
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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The tree shows the occurrence of this domain across different species. More...

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fer4 domain has been found. There are 261 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0P0Y344 View 3D Structure Click here
A0A1D6K1X2 View 3D Structure Click here
A0A1D6PB11 View 3D Structure Click here
A1ALP7 View 3D Structure Click here
A1E9X8 View 3D Structure Click here
A4HZ70 View 3D Structure Click here
A7H9V8 View 3D Structure Click here
B0SRH5 View 3D Structure Click here
D3ZD23 View 3D Structure Click here
D5AP15 View 3D Structure Click here
D5ARY6 View 3D Structure Click here
D5ARZ0 View 3D Structure Click here
G0SEV9 View 3D Structure Click here
H6LC27 View 3D Structure Click here
H6LGM8 View 3D Structure Click here
I1LIG5 View 3D Structure Click here
K7LWZ9 View 3D Structure Click here
K7MSH8 View 3D Structure Click here
O07835 View 3D Structure Click here
O27434 View 3D Structure Click here
O27719 View 3D Structure Click here
O27880 View 3D Structure Click here
O28002 View 3D Structure Click here
O28783 View 3D Structure Click here
O29309 View 3D Structure Click here
O29751 View 3D Structure Click here
O30274 View 3D Structure Click here
O33064 View 3D Structure Click here
O34720 View 3D Structure Click here
O50433 View 3D Structure Click here
O60102 View 3D Structure Click here
O67337 View 3D Structure Click here
O67386 View 3D Structure Click here
P00198 View 3D Structure Click here
P00207 View 3D Structure Click here
P00208 View 3D Structure Click here
P00218 View 3D Structure Click here
P00219 View 3D Structure Click here
P03942 View 3D Structure Click here
P07598 View 3D Structure Click here