Protein-sorting transpeptidase
A protein-sorting transpeptidase is an enzyme, such as the sortase SrtA[1] of Staphylococcus aureus, that cleaves one or more target proteins produced by the same cell, as part of a specialized pathway of protein targeting. The typical prokaryotic protein-sorting transpeptidase is characterized as a protease, but does not simply hydrolyze a peptide bond. Instead, the larger, N-terminal portion of the cleaved polypeptide is transferred onto another molecule, such as a precursor of the peptidoglycan cell wall in Gram-positive bacteria.
The term sortase is properly reserved for the set of cysteine protease enzymes sortase A, sortase B, and members of additional classes, all of which share homology. However, a growing number of additional protein sorting systems has been described in prokaryotes, involving sorting enzymes that lack any homology to sortase and that appear to have arisen separately by convergent evolution. Although the sortases are the best described members of the protein-sorting transpeptidases, work on the analogous enzymes archaeosortase,[2] rhombosortase,[3] and the PorU enzyme of type IX secretion systems (T9SS)[4] has been accumulating.
| sorting enzyme | mechanism | cognate sorting signal |
|---|---|---|
| sortase A | cysteine protease | LPXTG |
| sortase B | cysteine protease | NPQTN |
| archaeosortase A | cysteine protease | PGF-CTERM |
| exosortase A | cysteine protease | PEP-CTERM |
| rhombosortase | serine protease | GlyGly-CTERM |
| PorU as in Porphyromonas gingivalis | serine protease | T9SS C-terminal beta-sandwich domain |
Myxosortases, homologs of the type 2 CAAX prenyl protease Rce1, are analogous protein-sorting enzymes, but they are unlikely to function as transpeptidases. [5] It is likely, instead, that the cysteine residue in the target sequence is modified by a separate enzyme, and that modification is followed by cleavage by the myxosortase, as happens with Rce1. The exact biochemistry of the overall modification is not yet known.
References
[edit]- ^ Zong Y, Bice TW, Ton-That H, Schneewind O, Narayana SV (2004). "Crystal structures of Staphylococcus aureus sortase A and its substrate complex". J Biol Chem. 279 (30): 31383–9. doi:10.1074/jbc.M401374200. PMID 15117963.
- ^ Abdul Halim MF, Rodriguez R, Stoltzfus JD, Duggin IG, Pohlschroder M (2018). "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". Mol Microbiol. 108 (3): 276–287. doi:10.1111/mmi.13935. PMID 29465796.
- ^ Gadwal S, Johnson TL, Remmer H, Sandkvist M (2018). "C-terminal processing of GlyGly-CTERM containing proteins by rhombosortase in Vibrio cholerae". PLOS Pathog. 14 (10): e1007341. doi:10.1371/journal.ppat.1007341. PMC 6219818. PMID 30352106.
- ^ de Diego I, Ksiazek M, Mizgalska D, Koneru L, Golik P, Szmigielski B, et al. (2016). "The outer-membrane export signal of Porphyromonas gingivalis type IX secretion system (T9SS) is a conserved C-terminal β-sandwich domain". Sci Rep. 6: 23123. doi:10.1038/srep23123. PMC 4804311. PMID 27005013.
- ^ D. H. Haft: discovery of the myxosortases that process MYXO-CTERM and three novel prokaryotic C-terminal protein-sorting signals that share invariant Cys residues. In: Journal of bacteriology. Band 206, No. 1, January 2024, S. e0017323, doi:10.1128/jb.00173-23, PMID 38084967, PMC 1081000.