Diversity and Subcellular Distribution of Archaeal Secreted Proteins

Abstract

Secreted proteins make up a significant percentage of a prokaryotic proteome and play critical roles in important cellular processes such as polymer degradation, nutrient uptake, signal transduction, cell wall biosynthesis, and motility. The majority of archaeal proteins are believed to be secreted either in an unfolded conformation via the universally conserved Sec pathway or in a folded conformation via the Twin arginine transport (Tat) pathway. Extensive in vivo and in silico analyses of N-terminal signal peptides that target proteins to these pathways have led to the development of computational tools that not only predict Sec and Tat substrates with high accuracy but also provide information about signal peptide processing and targeting. Predictions therefore include indications as to whether a substrate is a soluble secreted protein, a membrane or cell wall anchored protein, or a surface structure subunit, and whether it is targeted for post-translational modification such as glycosylation or the addition of a lipid. The use of these in silico tools, in combination with biochemical and genetic analyses of transport pathways and their substrates, has resulted in improved predictions of the subcellular localization of archaeal secreted proteins, allowing for a more accurate annotation of archaeal proteomes, and has led to the identification of potential adaptations to extreme environments, as well as phyla-specific pathways among the archaea. A more comprehensive understanding of the transport pathways used and post-translational modifications of secreted archaeal proteins will also facilitate the identification and heterologous expression of commercially valuable archaeal enzymes.

S-layers: principles and applications

“…To enhance the stability of the composite SsLMs, head groups of phospholipids have been covalently linked to the S‐layer lattice (Schrems et al ., , b). Interestingly, it became evident that in nature, archaeal S‐layer proteins are targeted for post‐translational modifications such as the addition of a lipid (Kikuchi et al ., ; Konrad & Eichler, ; Szabo & Pohlschroder, ; Abdul Halim et al ., ). Hence, our approach to link lipids covalently to S‐layer proteins is a biomimetic one as lipid modifications of S‐layer glycoproteins are a general property of, for example, halophilic Archaea .…”

“…Recently, yet another post‐translational modification of S‐layer glycoproteins was reported. It could be demonstrated that a subset of secreted euryarchaeal proteins, including the S‐layer glycoprotein, is processed and covalently linked to membrane‐embedded lipids involving membrane‐spanning enzymes referred to as archaeosortases (Szabo & Pohlschroder, ; Eichler & Maupin‐Furlow, ). A distinctive subfamily of the archaeosortase/exosortase superfamily is designated archaeosortase A (ArtA) because of its restriction to the Archaea and its remote homology to exosortase.…”

Biomimetic interfaces based on S-layer proteins, lipid membranes and functional biomolecules

“…Recently, another type of binding of archaeal S-layer proteins to cytoplasmic membranes has been reported for Haloferax volcanii. It could be demonstrated that a subset of secreted euryarchaeal proteins, including the S-layer glycoprotein, is processed and covalently linked to membrane-embedded lipids involving membrane-spanning enzymes referred to as archaeosortases [45,46]. Because the C-terminal structure recognized by archaeosortases of a large number of euryarchaeal S-layer glycoproteins is highly conserved, it is very likely that this proposed lipid-anchoring mechanism is a broadly conserved surface-anchoring mechanism (figure 2b) [47][48][49].…”

“…Interestingly, it recently became evident that in nature archaeal proteins are targeted for post-translational modifications such as the addition of a lipid [46]. Hence, our approach to link lipids covalently to S-layer proteins is a biomimetic one occurring in archaea where a portion of membrane-bound proteins are anchored through a covalent association of their carboxy-termini with the lipid bilayer [47].…”

The modern “3G” age of archaeal molecular biology

“…This collection of 11 papers attempts to put this quiet maturation in archaeal molecular biology in context with a mix of overview articles (Atomi et al, 2012; Hileman and Santangelo, 2012; Kohler and Metcalf, 2012; Wagner et al, 2012) and original data (Bernick et al, 2012a,b; Iverson and Stedman, 2012; Mao and Grogan, 2012; Schut et al, 2012; Stroud et al, 2012; Szabo and Pohlschroder, 2012) highlighting the expansion of important areas enabled by the 3G's: genomics, genetics, and global collaboration. Research papers highlight the roles of small RNAs, CRISPR action, mechanisms of membrane secretion, hydrogen production, and DNA replication, while excellent technical overviews cover recently developed genetic methods within four major research communities utilizing Haloferax, Sulfolobus, Pyrococcus, or Thermococcus.…”