Diversity and functional plasticity of eukaryotic selenoproteins: Identification and characterization of the SelJ family

Abstract

Selenoproteins are a diverse group of proteins that contain selenocysteine (Sec), the 21st amino acid. In the genetic code, UGA serves as a termination signal and a Sec codon. This dual role has precluded the automatic annotation of selenoproteins. Recent advances in the computational identification of selenoprotein genes have provided a first glimpse of the size, functions, and phylogenetic diversity of eukaryotic selenoproteomes. Here, we describe the identification of a selenoprotein family named SelJ. In contrast to known selenoproteins, SelJ appears to be restricted to actinopterygian fishes and sea urchin, with Cys homologues only found in cnidarians. SelJ shows significant similarity to the jellyfish J1-crystallins and with them constitutes a distinct subfamily within the large family of ADP-ribosylation enzymes. Consistent with its potential role as a structural crystallin, SelJ has preferential and homogeneous expression in the eye lens in early stages of zebrafish development. A structural role for SelJ would be in contrast to the majority of known selenoenzymes. The unusually highly restricted phylogenetic distribution of SelJ, its specialization, and the comparative analysis of eukaryotic selenoproteomes reveal the diversity and functional plasticity of selenoproteins and point to a mosaic evolution of the use of Sec in proteins.ADP-ribosylation ͉ J1-crystallins ͉ selenocysteine ͉ selenium S elenocysteine (Sec) residues are found only in a small group of proteins called selenoproteins. Selenoproteins with characterized functions are enzymes involved in redox reactions. Sec is inserted by dynamic recoding of an in-frame UGA stop codon located upstream of the actual termination codon (1). Selenoproteins are present in eukaryotes and prokaryotes and, although their sets of selenoproteins (selenoproteomes) do not completely overlap (2), their intersection appears to be larger than previously thought (3). In eukaryotes, the Sec insertion sequence (SECIS), an RNA stem-loop located in the 3Ј UTR of selenoprotein genes, recruits several transacting factors to recode UGA from termination to Sec insertion (4). The dual function of this codon confounds genefinding programs and human curators, making selenoprotein identification a challenge (5-10).In addition, Cys and Sec are structurally related amino acids, with Sec incorporating selenium in the position of sulfur in Cys. The functional resemblance of Sec and Cys is supported by the observation that their residues occupy equivalent positions in homologous proteins. As expected, mutation of the Sec residue to Cys results in variants that are active but have a lower catalytic efficiency (11-13), although they may have an enhanced translation (13). Furthermore, natural Cys-containing counterparts are usually inferior catalysts (14, 15), but similar reactivity has also been reported (16). Hence, Sec, per se, does not possess an essential role in protein function and these two residues seem to be partially interchangeable. Accordingly, Sec and Cys residues are alte...

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

“…The hits include the JI jellyfish lens crystallins (29) and the zebrafish SelJ selenoprotein (30), indicating that the ARH fold may have been adopted to also serve structural functions. It is interesting to note, however, that neither PSI-BLAST nor secondary-structure prediction analyses revealed any sequence or structural resemblance of PARG to the ARH3͞DRAG protein family (28).…”

Effects of dietary selenium nanoparticles on physiological andbiochemical aspects of juvenile Tor putitora

“…GSH-Px is the most important selenoenzyme that plays an important role in all animal cells, because when it is in a reduced state, it decreases the production of lipid hydroperoxides and hydrogen peroxides near the cytosol and mitochondrial milieu (Dong, 2000). Thus, it provides protection to the organism against oxygen free radicals produced during stressful conditions or when an animal is exposed to certain kinds of toxicity (Beckett and Arthur, 2005;Castellano et al, 2005).…”

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“…A single SECIS element is sufficient to dictate Sec incorporation in all selenoproteins with the exception of SelP, which contains two SECIS elements that direct the decoding of 10 UGA-Sec codons in mammals and up to 17 in fish (59). The mechanism appears even more complicated, as SelP occurs in four different isoforms that arise from translation…”

“…Between the domains, 30 selenoprotein families have been identified (59,184,185,348). Selenoproteomes among species are generally small; the largest repertoire exists in fish with 30 individual selenoproteins, followed by humans and rodents with 25 and 24 selenoproteins, respectively (59). Their small size can be explained by a limited selenium supply in nature and a rather energy-expensive synthesis process.…”

“…Yeast and higher plants lack selenoproteins and the components required for their synthesis; however, they do express cysteine (Cys)-containing homologues (184). For most selenoprotein families, Sec/Cys interconversion is commonly observed across the species (59). The human selenoproteome consists of 17 selenoprotein families, some with multiple genes with similar functions (184).…”