archaeosortase

{{Short description|Protein family}}

An archaeosortase is a protein that occurs in the cell membranes of some archaea.{{cite journal|last=Haft|first=Daniel H. |author2=Samuel H. Payne |author3=Jeremy D. Selengut|title=Archaeosortases and Exosortases Are Widely Distributed Systems Linking Membrane Transit with Posttranslational Modification|journal=J. Bacteriol.|date=January 2012|volume=194|issue=1|pages=36–48|doi=10.1128/JB.06026-11|url= |pmid=22037399|pmc=3256604}} Archaeosortases recognize and remove carboxyl-terminal protein sorting signals about 25 amino acids long from secreted proteins. A genome that encodes one archaeosortase may encode over fifty target proteins. The best characterized archaeosortase target is the Haloferax volcanii S-layer glycoprotein, an extensively modified protein with O-linked glycosylations, N-linked glycosylations, and a large prenyl-derived lipid modification toward the C-terminus.{{cite journal|title=Haloferax volcanii archaeosortase is required for motility, mating, and C-terminal processing of the S-layer glycoprotein|pmid=23651326 | doi=10.1111/mmi.12248 | volume=88|issue=6|date=Jun 2013|pages=1164–75|journal=Mol Microbiol|last1=Abdul Halim |first1=Mohd Farid |last2=Pfeiffer |first2=Friedhelm |last3=Zou |first3=James |last4=Frisch |first4=Andrew |last5=Haft |first5=Daniel |last6=Wu |first6=Si |last7=Tolić |first7=Nikola |last8=Brewer |first8=Heather |last9=Payne |first9=Samuel H. |last10=Paša-Tolić |first10=Ljiljana |last11=Pohlschroder |first11=Mechthild |s2cid=5756916 }} 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.{{cite journal|title=Permuting the PGF Signature Motif Blocks both Archaeosortase-Dependent C-Terminal Cleavage and Prenyl Lipid Attachment for the Haloferax volcanii S-Layer Glycoprotein.|pmid=26712937 | doi=10.1128/JB.00849-15 | volume=198|year=2016|journal=J. Bacteriol.|pages=808–15 | last1 = Abdul Halim | first1 = MF | last2 = Karch | first2 = KR | last3 = Zhou | first3 = Y | last4 = Haft | first4 = DH | last5 = Garcia | first5 = BA | last6 = Pohlschroder | first6 = M|issue=5 |pmc=4810604}} Thus archaeosortase appears to be a transpeptidase, like sortase, rather than a simple protease.

Archaeosortases are related to exosortases, their uncharacterized counterparts in Gram-negative bacteria. The names of both families of proteins reflect roles analogous to sortases in Gram-positive bacteria, with which they share no sequence homology. 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. Replacement of either destroys catalytic activity, suggesting convergent evolution of the active site with the sortases.{{cite journal | vauthors = Abdul Halim MF, Rodriguez R, Stoltzfus JD, Duggin IG, Pohlschroder M | title = Conserved residues are critical for Haloferax volcanii archaeosortase catalytic activity: Implications for convergent evolution of the catalytic mechanisms of non-homologous sortases from archaea and bacteria | journal = Molecular Microbiology | volume = 108 | issue = 3 | pages = 276–287 | date = May 2018 | pmid = 29465796 | doi = 10.1111/mmi.13935 | doi-access =free }}

In the archaeal model species Haloferax volcanii, 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 RhoII, and in contrast to bacterial sortases.{{cite journal | vauthors = Giménez MI, Cerletti M, De Castro RE | title = Archaeal membrane-associated proteases: insights on Haloferax volcanii and other haloarchaea | journal = Frontiers in Microbiology | volume = 6 | pages = 39 | date = 2015 | pmid = 25774151 | pmc = 4343526 | doi = 10.3389/fmicb.2015.00039 | doi-access = free }}