Archaeosortase
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An archaeosortase is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that occurs in the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s of some
archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
. Archaeosortases recognize and remove carboxyl-terminal
protein sorting :''This article deals with protein targeting in eukaryotes unless specified otherwise.'' Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the ce ...
signals about 25 amino acids long from secreted proteins. A
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
that encodes one archaeosortase may encode over fifty target proteins. The best characterized archaeosortase target is the
Haloferax In taxonomy, ''Haloferax'' (common abbreviation: ''Hfx.'') is a genus of the Haloferacaceae. Genetic exchange Cells of ''H. mediterranei'' and cells of the related species '' H. volcanii'' can undergo a process of genetic exchange between two c ...
volcanii
S-layer An S-layer (surface layer) is a part of the cell envelope found in almost all archaea, as well as in many types of bacteria. The S-layers of both archaea and bacteria consists of a monomolecular layer composed of only one (or, in a few cases, two) i ...
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
, an extensively modified protein with O-linked glycosylations, N-linked glycosylations, and a large prenyl-derived lipid modification toward the C-terminus. Knockout of the archaeosortase A (artA) gene, or permutation of the motif Pro-Gly-Phe (PGF) to Pro-Phe-Gly in the S-layer glycoprotein, blocks attachment of the lipid moiety as well as blocking removal of the PGF-CTERM protein-sorting domain. Thus archaeosortase appears to be a transpeptidase, like
sortase Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any ...
, rather than a simple
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
. Archaeosortases are related to
exosortase Exosortase refers to a family of integral membrane proteins that occur in Gram-negative bacteria that recognizes and cleaves the carboxyl-terminal sorting signal PEP-CTERM. The name derives from a predicted role analogous to sortase, despite the ...
s, their uncharacterized counterparts in
Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
. The names of both families of proteins reflect roles analogous to
sortase Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any ...
s in
Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
, with which they share no
sequence homology Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...
. The sequences of archaeosortases and exosortases consists mostly of hydrophobic transmembrane helices, which sortases lack. Archaeosortases fall into a number of distinct subtypes, each responsible for recognizing sorting signals with a different signature motif. Archaeosortase A (ArtA) recognizes the PGF-CTERM signal, ArtB recognizes VPXXXP-CTERM, AtrC recognizes PEF-CTERM, and so on; one archaeal genome may encode two different archaeosortase systems. Invariant residues shared by all archaeosortases and exosortases include a Cys and an
Arg Arg or ARG may refer to: Places *''Arg'' () means "citadel" in Persian, and may refer to: **Arg, Iran, a village in Fars Province, Iran **Arg (Kabul), presidential palace in Kabul, Afghanistan **Arg, South Khorasan, a village in South Khorasan P ...
. Replacement of either destroys catalytic activity, suggesting
convergent evolution Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last com ...
of the
active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
with the sortases. In the archaeal model species
Haloferax volcanii ''Haloferax volcanii'' is a species of organism in the genus ''Haloferax'' in the Archaea. Description and significance Microbiologist Benjamin Elazari Volcani first discovered ''Haloferax volcanii'', a self-named extremophile, in the 1930s. '' ...
, archaeosortase A belongs to a fairly large collection of identified membrane-associated proteases, but apparently also to the smaller set of intramembrane cleaving proteases, along with the
rhomboid protease The rhomboid proteases are a family of enzymes that exist in almost all species. They are proteases: they cut the polypeptide chain of other proteins. This proteolytic cleavage is irreversible in cells, and an important type of cellular regulatio ...
RhoII, and in contrast to bacterial sortases.


References

{{reflist Membrane proteins * Proteases