9.B.297.  The Archaeosortase/Exosortase/Rhomosortase/Cyanosortase (Sortase) Family 

Integral membrane archaeosortases recognize and remove carboxyl-terminal protein targetting signals about 25 amino acids long from secreted proteins (Haft et al. 2012). A genome that encodes one archaeosortase may encode over fifty target proteins. The best characterized archaeosortase target is the Halofax volcanii S-layer glycoprotein, an extensively modified protein withO- and N-linked glycosylations as well as a large prenyl-derived lipid modification toward the C-terminus (Abdul Halim et al. 2013). 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 (Abdul Halim et al. 2015). 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 lack significant sequence similarity. The sequences of archaeosortases and exosortases consists mostly of hydrophobic transmembrane helices, which sortases lack (Abdul Halim et al. 2018). 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, ArtC recognizes PEF-CTERM, and so on; one archaeal genome may encode two different archaeosortase systems (Giménez et al. 2015).