Biochimica et Biophysica Acta (BBA) - General Subjects
ReviewSelenoprotein synthesis and regulation in Archaea☆
Introduction
The element selenium was discovered in 1817 [1] and for the longest time regarded as toxic. However, in 1954 it was shown that E. coli required selenium for the synthesis of enzymes involved in formate oxidation [2], which hallmarks the role of this trace element for microbial metabolism. Today we know that selenium is essential for many organisms, including humans [3]. Biologically active selenium occurs (i) as a constituent of a base modification (5-[(methylamino)methyl]-2-selenouridine) in certain transfer RNAs (tRNAs, [4]), (ii) as a non-covalently bound selenium-containing cofactor found in xanthine and nicotinate dehydrogenases [5,6], and (iii) as the co-translationally inserted amino acid selenocysteine (Sec, 2-selenoalanine). As the name suggests, it is structurally identical to cysteine (Cys), only with the thiol group replaced by a selenol group.
The occurrence of Sec as the selenium moiety in naturally occurring proteins (selenoproteins) was first demonstrated in clostridial glycine reductase [7]. Selenoproteins are found in members of all three domains of life, the Bacteria, the Archaea, and the Eukarya. However, the majority of known organisms do not employ Sec. Since various aspects of this trait have been conserved in the three domains of life (see below), Sec was probably already present in the last universal common ancestor (LUCA) [[8], [9], [10]]. For most selenoproteins the specific functions of Sec are still unclear, because for all but one of the selenoproteins of prokaryotes (clostridial glycine reductase) homologous proteins with Cys at the respective position exist [11]. Consequently, there is currently only little evidence for natural positive selection in any single Sec residue [12]. The fact that the selenol group is mostly deprotonated at physiological pH due to its lower pka value (5.2 for Sec, 8.3 for Cys) might make it more reactive than Cys. Other physico-chemical properties of Sec possibly favor some selenoproteins over their Cys variants [[13], [14], [15], [16]] but a unifying principle encompassing all selenoproteins has, so far, not emerged and may simply not exist.
In this review we aim to summarize current knowledge about the selenoproteins in Archaea, the pathway of Sec synthesis and incorporation into proteins, as well as selenium-dependent gene regulation. Although many still consider Archaea as a “strange bacteria”, they were vital for progressing knowledge about Sec synthesis and incorporation in the eukaryal system. Many members of the Archaea have been developed into powerful genetic model systems [17]. Given the current discussion about the phylogenetic relation of Eukarya and Archaea within the tree of life [18], they may be highly valuable tools for unraveling other eukaryotic “secrets” in the future.
Section snippets
Commonalities of selenoprotein synthesis in the three domains
Unlike canonical translation elongation, where amino acids are acylated to their corresponding tRNAs by aminoacyl-tRNA synthetases, Sec is always synthesized in a tRNA-bound fashion. The Sec-specific tRNA (tRNASec) differs from canonical elongator tRNAs in size and structural interactions (see below) and is in all known cases initially “mis-charged” with serine (Ser) by seryl-tRNA synthetase. The pathways of conversion from Ser-tRNASec to Sec-tRNASec differ between Bacteria on the one hand and
A methanogenic origin of the Sec utilization trait in eukaryotes?
Based on the analysis of ribosomal RNA, “Archaebacteria” were postulated to comprise one of three “urkingdoms” some 40 years ago [20], now known as the domains Bacteria, Eukarya, and Archaea [21]. At the time, the presumed “archaic” life-style of Archaea, being strictly anaerobic and/or inhabiting inhospitable environments like solfataric hot springs, soda lakes, and submarine volcanic vents, may have led to this tendentious designation. However, Archaea are ubiquitous and constitute a
Methanogenesis
Methane is the most abundant hydrocarbon present in our atmosphere. In environments lacking electron acceptors such as oxygen, sulfate, nitrate, or oxidized metal(loid)s, methane is the final breakdown product of organic matter. This process, anaerobic digestion, which is carried out by microorganisms of various trophic groups, can be categorized into four steps: (i) hydrolysis of the polymeric matter into oligomers and monomers, (ii) fermentation of the monomers (sugars, amino acids, fatty
Most selenoproteins of Archaea are involved in methanogenesis
As of 2017, where 498 archaeal (meta-)genomes were analyzed, 21 encode tRNASec [40]. 19 of the respective organisms belong to the order Methanococcales (genera Methanocaldococcus, Methanotorris, Methanothermococcus, Methanococcus), one to the order Methanopyrales (genus Methanopyrus), and one to the uncultivated, proposed archaeal phylum Lokiarchaeota (see above). Table 1 lists known and putative archaeal selenoproteins and their properties (where known) are summarized in the following section.
Selenoprotein synthesis in Archaea
Considering that the ability to use Sec appears to be so asymmetrically distributed among the Archaea [40], it was a fortuitous coincidence that the first genome sequence published from this domain was that of Methanocaldococcus jannaschii [96]. It allowed the identification of putative selenoproteins as well as of some of the cis- and trans-active factors involved in their synthesis [89].
Selenium-dependent gene regulation
The dependence on selenium varies considerably among Sec-encoding methanogens. However, the experimental verification of selenium requirement is difficult, because of contaminating selenium present in (sodium) sulfide used as sulfur source and as a means to provide the strongly reduced conditions required by methanogens [130,162]. Growth of M. jannaschii depends on the presence of selenium [163], that of M. voltae is reduced when the selenium supply is limiting [162], while no effect on
Conclusions
It has been argued that eukaryotes “re-invented” the Sec utilization trait during evolution because their Sec-containing oxidoreductases, mostly involved in antioxidant defense and redox homeostasis, are so different from the selenoproteins of Bacteria and Archaea, which are mostly catabolically active and seem unrelated to the eukaryotic ones. However, this view might be challenged by the finding that an archaeal selenoprotein (HdrA) involved in a very ancient metabolism (methanogenesis)
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Acknowledgements
We thank Miljan Simonović (Chicago, USA) for sharing his contribution to this special issue prior to publication, Tristan Wagner (Marburg, Germany) for fruitful discussions about the possible role of Sec in methanogenic enzymes, and the Deutsche Forschungsgemeinschaft for supporting work in the authors' laboratory (RO 2445/7-1).
References (177)
- et al.
Functional diversity of the rhodanese homology domain: the Escherichia coli ybbB gene encodes a selenophosphate-dependent tRNA 2-selenouridine synthase
J. Biol. Chem.
(2004) Selenoproteins — what unique properties can arise with selenocysteine in place of cysteine?
Exp. Cell Res.
(2010)Anaerobic oxidation of methane with sulfate: on the reversibility of the reactions that are catalyzed by enzymes also involved in methanogenesis from CO2
Curr. Opin. Microbiol.
(2011)- et al.
Bioenergetics and anaerobic respiratory chains of aceticlastic methanogens
Biochim. Biophys. Acta
(2014) Formate dehydrogenase
FEMS Microbiol. Rev.
(1990)- et al.
Selenium-dependent and selenium-independent formate dehydrogenases of Methanococcus vannielii. Separation of the two forms and characterization of the purified selenium-independent form
J. Biol. Chem.
(1981) - et al.
Classification and phylogeny of hydrogenases
FEMS Microbiol. Rev.
(2001) - et al.
Nickel uptake and utilization by microorganisms
FEMS Microbiol. Rev.
(2003) The structure and mechanism of iron-hydrogenases
Biochim. Biophys. Acta
(1990)- et al.
The crystal structure of a reduced [NiFeSe] hydrogenase provides an image of the activated catalytic center
Structure
(1999)
A selenium-containing hydrogenase from Methanococcus vannielii. Identification of the selenium moiety as a selenocysteine residue
J. Biol. Chem.
Crystal structure of IscA, an iron-sulfur cluster assembly protein from Escherichia coli
J. Mol. Biol.
Characterization of a mammalian peroxiredoxin that contains one conserved cysteine
J. Biol. Chem.
Escherichia coli mutant SELD enzymes. The cysteine 17 residue is essential for selenophosphate formation from ATP and selenide
J. Biol. Chem.
Biochemical analysis of Escherichia coli selenophosphate synthetase mutants. Lysine 20 is essential for catalytic activity and cysteine 17/19 for 8-azido-ATP derivatization
J. Biol. Chem.
Structure of selenophosphate synthetase essential for selenium incorporation into proteins and RNAs
J. Mol. Biol.
Selenoprotein synthesis in Archaea: identification of an mRNA element of Methanococcus jannaschii probably directing selenocysteine insertion
J. Mol. Biol.
Selenocysteine inserting tRNAs: an overview
FEMS Microbiol. Rev.
Undersökning af en ny Mineral-kropp, funnen i de orenare sorterna af det i Falun tillverkade svaflet, Afhandlingar i fysik, kemi och mineralogi 6
The need for selenite and molybdate in the formation of formic dehydrogenase by members of the coli-aerogenes group of bacteria
Biochem. J.
Selenoproteins and selenoproteomes
Nicotinic acid hydroxylase from Clostridium barkeri: electron paramagnetic resonance studies show that selenium is coordinated with molybdenum in the catalytically active selenium-dependent enzyme
Proc. Natl. Acad. Sci. U. S. A.
Orphan SelD proteins and selenium-dependent molybdenum hydroxylases
Biol. Direct
Chemical characterization of the selenoprotein component of clostridial glycine reductase: identification of selenocysteine as the organoselenium moiety
Proc. Natl. Acad. Sci. U. S. A.
RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea
Proc. Natl. Acad. Sci. U. S. A.
Dynamic evolution of selenocysteine utilization in bacteria: a balance between selenoprotein loss and evolution of selenocysteine from redox active cysteine residues
Genome Biol.
Evolution of selenium utilization traits
Genome Biol.
High-throughput identification of catalytic redox-active cysteine residues
Science
Evolutionary basis for the use of selenocysteine
Selenium in chemistry and biochemistry in comparison to sulfur
Biol. Chem.
Selenocysteine confers resistance to inactivation by oxidation in thioredoxin reductase: comparison of selenium and sulfur enzymes
Biochemistry
Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis
Cell
Model organisms for genetics in the domain Archaea: methanogens, halophiles, Thermococcales and Sulfolobales
FEMS Microbiol. Rev.
Archaea and the origin of eukaryotes
Nat. Rev. Microbiol.
Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3′ untranslated region
Nature
Phylogenetic structure of the prokaryotic domain: the primary kingdoms
Proc. Natl. Acad. Sci. U. S. A.
Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya
Proc. Natl. Acad. Sci. U. S. A.
Environmental diversity of bacteria and archaea
Syst. Biol.
General characteristics and important model organisms
The growing tree of Archaea: new perspectives on their diversity, evolution and ecology
ISME J.
Methane metabolism in the archaeal phylum Bathyarchaeota revealed by genome-centric metagenomics
Science
Methylotrophic methanogenesis discovered in the archaeal phylum Verstraetearchaeota
Nat. Microbiol.
The two-domain tree of life is linked to a new root for the Archaea
Proc. Natl. Acad. Sci. U. S. A.
Methanogenesis and the Wood-Ljungdahl pathway: an ancient, versatile, and fragile association
Genome Biol. Evol.
Complex archaea that bridge the gap between prokaryotes and eukaryotes
Nature
Asgard archaea illuminate the origin of eukaryotic cellular complexity
Nature
An archaeal origin of eukaryotes supports only two primary domains of life
Nature
Lokiarchaeota marks the transition between the archaeal and eukaryotic selenocysteine encoding systems
Mol. Biol. Evol.
Methanogenic archaea: ecologically relevant differences in energy conservation
Nat. Rev. Microbiol.
Methanogenesis
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2023, Current Research in BiotechnologyCitation Excerpt :This strain is the nomenclatural type of species and was widely studied before the sequence of strain S2 became available. It is characterized by its robust autotrophic growth and has proven to be an important model for selenium metabolism (Rother and Quitzke 2018). Its genome was sequenced in 2018 (Poehlein et al. 2018).
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2022, Free Radical Biology and MedicineCitation Excerpt :As it constitutes the selenoprotein family with the most diverse phylogenetic distribution, selD/SPS2 can illustrate these differences well, as this family contains instances of all SECIS versions (Fig. 4). This includes the bacterial SECIS [57,58], the canonical archaeal SECIS characterized in methanogens [59,60], the Lokiarchaeota SECIS [61], and the eukaryotic SECIS [62,63]. The SECIS in eukaryotic SelD/SPS2 is of “type II”, meaning that it presents a third stem in the apical loop region which is missing from “type I″ SECIS elements [58,64].
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2022, Methods in EnzymologyCitation Excerpt :The price to pay for the use of Sec in an enzyme is high if considering the highly intricate, energy demanding and often inefficient translation machinery that is required for expression of a selenoprotein. There are qualitative differences between these translation machineries between the kingdoms of life, and between organisms, but all involve the use of a dedicated elongation factor specific for Sec insertion through the recoding of a UGA stop codon, achieved via interactions with a stem loop structure in the selenoprotein-encoding mRNA (a SECIS structure), use of a specific tRNA with an anticodon to the UGA that is originally serylated with the seryl moiety subsequently converted to selenocysteinyl on the tRNA, and a variety of accessory enzymes and factors supporting this translation machinery that is only used for the insertion of a Sec residue in a growing polypeptide chain at the ribosome (Allmang, Wurth, & Krol, 2009; Brocker et al., 2014; Driscoll & Copeland, 2003; Gursinsky et al., 2008; Lescure et al., 2002; Rother & Quitzke, 2018; Yoshizawa & Böck, 2009). This is thus a most complicated translation machinery, with species-specific variations, inefficiency on a cellular level compared to expression of most regular non-selenoproteins, and high complexity, further complicated by the inherent high chemical reactivity of Sec (indeed itself a possible reason why its synthesis has evolved to be so complicated, possibly as a means of controlling the reactivity of Sec that would otherwise lead to uncontrolled redox reactions in cells).
Green synthesis of selenium-N-heterocyclic carbene compounds: Evaluation of antimicrobial and anticancer potential
2019, Bioorganic ChemistryCitation Excerpt :Selenium containing compounds are promising candidates for cancer therapy due to their ability to alter various physiological functions involved in cancer development, presenting either anticancer, antimicrobial, antioxidant, anti-inflammatory, anti-viral, anti-neurodegenerative, anti-depressant, anti-neoplastic and chemo preventive activities [1–18]. Selenium is essential micronutrient [9,19–21] which is non-toxic to humans in low concentrations, therefore an adduct that releases selenium to the biological system in a steady rate act as an effective pharmaceutical agent [22]. The effectiveness of selenium adducts as an anti-infective agent depends on the bioavailability of selenium at the site of action [23].
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This article is part of a Special Issue entitled Selenium research in biochemistry and biophysics - 200 year anniversary issue, edited by Dr. Elias Arnér and Dr. Regina Brigelius-Flohe.