Posttranslational protein modification in Archaea

Abstract

One of the first hurdles to be negotiated in the postgenomic era involves the description of the entire protein content of the cell, the proteome. Such efforts are presently complicated by the various posttranslational modifications that proteins can experience, including glycosylation, lipid attachment, phosphorylation, methylation, disulfide bond formation, and proteolytic cleavage. Whereas these and other posttranslational protein modifications have been well characterized in Eucarya and Bacteria, posttranslational modification in Archaea has received far less attention. Although archaeal proteins can undergo posttranslational modifications reminiscent of what their eucaryal and bacterial counterparts experience, examination of archaeal posttranslational modification often reveals aspects not previously observed in the other two domains of life. In some cases, posttranslational modification allows a protein to survive the extreme conditions often encountered by Archaea. The various posttranslational modifications experienced by archaeal proteins, the molecular steps leading to these modifications, and the role played by posttranslational modification in Archaea form the focus of this review.

FIG. 1.

Schematic depiction of the glycosylation of the Halobacterium salinarum S-layer glycoprotein. The topology of the S-layer glycoprotein, the positions of the 11 Asn residues that undergo N-glycosylation, and the heavily O-glycosylated Thr-rich region between Thr-755 and Thr-779 are indicated (246). The inset shows the composition of the three oligosaccharide moieties bound to the protein (247). Abbreviations used: G, glucose; GA, glucaronic acid; Gal, galactose; GalA, galacturonic acid; Galf, galactofuranose; GalN, N-acetylgalactosamine; GN, N-acetylglucosamine; OMe, O-methyl; SO₄, sulfate. Approximately a third of the glucaronic acid residues may be replaced by iduronic acid.

FIG. 2.

Schematic depiction of archaeal N-glycosylation. Step 1. A dolichol pyrophosphate (or monophosphate) species is glycosylated by transfer of saccharide subunits from nucleotide sugars (or possibly from lipid-bound sugar precursors). Step 2. Glycosylated phosphodolichol “flips” across the plasma membrane, likely in an enzyme-mediated process. Step 3. The oligosaccharide structure is transferred to selected Asn residues of a newly translocated polypeptide. The figure does not consider the relationship between protein translation and protein translocation or the relationship between protein translocation and protein glycosylation. Step 4. Following transfer of the oligosaccharide moiety to a protein target, the phosphorylated dolichol carrier is recycled to its original topology. See references 247, 420, and 468, the text, and Table 3 for additional information.

FIG. 3.

Schematic depiction of two Archaeoglobus fulgidus gene clusters putatively involved in protein glycosylation. Putative gene products are given above each ORF. For further details, see reference 46.

FIG. 4.

Schematic depiction of representative archaeal lipid-modified proteins. Shown are Natronobacterium pharaonis halocyanin and Halobacterium salinarum S-layer glycoprotein. The lipid modification and acetylation of the amino-terminal Cys of Natronobacterium pharaonis halocyanin have not been experimentally proven, nor has the linkage or exact position of the diphytanylglycerylphosphate group found within the Thr-rich carboxy-terminal region of the Halobacterium salinarum S-layer glycoprotein. See text for details.

FIG. 5.

Methylated amino acids in Methanobacterium thermoautotrophicum methyl-coenzyme M reductase. A. 2-(S)-Methylglutamine. B. S-Methylcysteine. C. 5-(S)-Methylarginine. D. 1-N-Methylhistidine. In each case, the modifying methyl group is boxed.

FIG. 6.

Schematic depiction of archaeal signal sequences. In each case, consensus sequence elements characteristic of that class of signal sequence are shown, where + corresponds to positively charged residues, x corresponds to any residue, and φ corresponds to a hydrophobic residue. Hydrophobic stretches of amino acid residues are portrayed in gray. The site of cleavage is denoted by the black wedge.