Table 1.
Predicted membrane proteases of represtenative archaeal genomes.
| Protease name | MEROPS family | Cleavage site | Topology | Description | Organism | Reference |
|---|---|---|---|---|---|---|
| Signal peptidases (SP) | Cleaves signal peptides of preproteins | |||||
| SPI | S26B | Active site on external face of cytoplasmic membrane | Resemble eukaryotic SPI. Cleaves the majority of signal peptides from preproteins exported by Sec (Tat?) system | |||
| SPI (MJ0260) | 2 TMS | First SPI characterized from archaea | Methanococcus voltae | Ng and Jarrell (2003); Ng et al. (2007) | ||
| Sec11a (HVO_2603); Sec11b (HVO_0002) | 1 TMS | Both active in vitro, different efficiency for substrate cleavage. Sec11b is essential for viability | Haloferax volcanii | Fine et al. (2006); Fink-Lavi and Eichler (2008) | ||
| TFPP-like (SPIII) | Active site on internal face of cytoplasmic membrane | Novel family of aspartyl proteases (GxGD). Cleaves signal peptides of preflagellins prior to incorporation into the archaellum | ||||
| PibD (SSO0131) | A24 | 5 TMS | Broad substrate range. Cleaves signal peptides of preflagellins and sugar-binding proteins (“bindosome”) | Sulfolobus solfataricus | Albers et al. (2003, 2006); Szabo et al. (2006); Ng et al. (2009) | |
| (Saci_0139) | 6 TMS | In vivo activity assays led to redefine PibD as GxHyD (Hy = hydrophobic residue) rather than a GxGD group of proteases | Sulfolobus acidocaldarius | Henche et al. (2014) | ||
| (HVO_2993) | 6 TMS | Cleaves preflagellins and type IV pilin-like proteins. Required for swimming motility (flagella) and surface adhesion (type IV pili-like structures) | H. volcanii | Tripepi et al. (2010) | ||
| EppA (MMP0232, MJ0835.2) | A24A | 9–10 TMS | Cleaves signal peptides of pilin-like proteins containing a DUF361 domain | Methanococcus maripaludis, Methanococcus jannaschii | Szabo et al. (2007) | |
| FlaK (Mvol_0164) | A24B | 5 TMS | Inactivation of FlaK generates non- flagellated cells. Residues Ser52, His122 and Asp148 crucial for protease activity | M. voltae | Bardy and Jarrell (2003); Bardy et al. (2005) | |
| (MMP0555) | 5 TMS | Displays preflagellin peptidase activity. placeCityCrystal structure is available | M. maripaludis | Bardy and Jarrell (2002); Hu et al. (2011) | ||
| Signal peptide peptidases (SPP) | Degrades signal peptides after removal by SP | |||||
| SppA (TK1164) | S49 | Active site at the soluble extracytoplasmic side | 1 TMS | First insight into catalytic mechanism of prokaryotic SPPs | Thermococcus kodakaraensis | Matsumi et al. (2005, 2006) |
| Presenilin/SPP homolog | A22 | Active site at the membrane plane (ICliP) | Regulatory intramembrane proteolysis (RIP). Aspartyl proteases (GxGD) | |||
| PSH; MCMJR1 peptidase | 9 TMS | Crystal structure determined in an archaeon. Insights on catalytic mechanism of Presenilin and SPP intramembrane proteases | Methanoculleus marisnigri | Li et al. (2013) | ||
| ATP-dependent proteases | Protein quality control. Regulatory proteases | |||||
| LonB | S16 | ATPase and protease domains facing cytoplasm | ||||
| (TK1264) | 2 TMS | ATP-independent activity on unfolded substrates; ATP-dependent activity on folded proteins | T. kodakaraensis | Fukui et al. (2002) | ||
| (Ta1081) | 2 TMS | Confirmation of S-K catalytic dyad. Recombinant LonB protease showed ATPase and protease activities | Thermoplasma acidophilium | Besche and Zwickl (2004); Besche et al. (2004) | ||
| (AF0364) | 1 TMS | Crystal structure of LonB proteolytic domain solved | Archaeoglobus fulgidus | Botos et al. (2005) | ||
| (TON_0529) | 2 TMS | Crystal structure 2.0- resolution solved | Thermococcus onnurineus | Cha et al. (2010) | ||
| (Nmag_2822) | 2 TMS | DNA-binding capacity in vitro. Can complement a LonB mutant in H. volcanii suggesting functional conservation of LonB | Natrialba magadii | Sastre et al. (2011); Cerletti et al. (2014) | ||
| (HVO_0783) | 2 TMS | Essential for viability. Quality control of proteins. Suboptimal LonB expression affects the content of membrane carotenoids and other lipids | H. volcanii | Cerletti et al. (2014) | ||
| Rhomboids | S54 | Active site at the membrane plane (ICliP) | Regulatory intramembrane proteolysis (RIP) | |||
| Rho II (HVO_ 0727) | 6 TMS | A null mutant in rhoII gene showed reduced mobility and higher sensitivity to novobiocin. The mutation affected N-glycosylation of the S-layer glycoprotein with a sulfoquinovose containing oligosaccharide | H. volcanii | Parente et al. (2014) | ||
| Site 2 proteases (S2P) | M50B | Active site at the membrane plane (ICliP) | Regulatory intramembrane proteolysis (RIP) | |||
| (MJ_0392) | 6 TMS | The crystal structure of the transmembrane core was determined (3B4R) | M. jannaschii | Feng et al. (2007) | ||
| Archaeosortases | N/A | Predicted active-site Cys oriented toward the extracellular side | ||||
| (HVO_0915) | 7 TMS | Involved in C-terminal processing of the S-layer glycoprotein | H. volcanii | Abdul Halim et al. (2013) | ||
| Thermopsine (SSO2194) | A5 | Active site oriented to the extracellular milieu | 1 TMS | Overproduced in peptide enriched media. Catalytic domain followed by PKD and Y_Y_Y domains | S. solfataricus | Cannio et al. (2010) |
| CAAX prenyl proteases | M79 | In eukaryotic cells they are involved in prenylation of proteins for membrane localization | ||||
| Abi (HVO_0784) | 5 TMS | Putative CAAX protease homolog. Forms a transcription unit with lonb gene. A null mutant showed no evident phenotypes | H. volcanii | Cerletti et al. (2014) |