Metacaspase Explained

Metacaspases are members of the C14 class of cysteine proteases and thus related to caspases, orthocaspases and paracaspases.^[1] The metacaspases are arginine/lysine-specific, in contrast to caspases, which are aspartate-specific.^[2]

Structure and Phylogenetic distribution

Prokaryotes

In archea and bacteria, there are several metacaspases with a wide range of domain organizations.^[3] Based on the prokaryote metacaspase diversity, orthocaspases can be considered a sub-class of metacaspases. Common for both metacaspases and orthocaspases classes is their specificity for basic residues (arginine or lysine) in the P1 position. At this moment, no structural variants have been reported where the substrate specificity would change to an acidic residue (aspartic acid), like in true caspases.

Eukaryotes

Metacaspases are found in plants, fungi, and "protists", but not in slime mold or animals.

Viruses

Viral metacaspases, which may have implications in rewiring host metabolism to enhanceinfection, are widespread in the ocean.^[4]

Type I

Type I metacaspases are characterized by an amino-terminal proline or glutamine rich LSD zinc finger-like domain.^[5] This type can be found in prokaryotes and eukaryotes other than animals.

Type II

Type II is found only in certain green algae and land plants, with one recent exception where both type I and type II metacaspases were found in the genome of Monosiga brevicollis (Choanoflagellate),^[6] possibly as a result of an unusual horizontal gene transfer between two eukaryotes.This group is characterized by long linker region and the absence of an amino-terminal pro-domain.

Known functions

In an analogous manner to caspases, metacaspases induce programmed cell death in both plants and fungi (yeast).^{[7] [8] [9]}

See also

• The Proteolysis Map
• MALT1

Notes and References

1. Uren AG, O'Rourke K, Aravind LA, etal . Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma . Molecular Cell . 6 . 4 . 961–7 . Oct 2000 . 11090634 . 10.1016/S1097-2765(05)00086-9. free .
2. Vercammen D, van de Cotte B, De Jaeger G, etal . Type II metacaspases Atmc4 and Atmc9 of Arabidopsis thaliana cleave substrates after arginine and lysine . J Biol Chem . 279 . 44 . 45329–36 . Oct 2004 . 15326173 . 10.1074/jbc.M406329200 . free .
3. Asplund-Samuelsson J, Bergman B, Larsson J . Prokaryotic caspase homologs: phylogenetic patterns and functional characteristics reveal considerable diversity. . PLOS ONE . 7 . 11 . e49888 . Nov 2012 . 23185476 . 10.1371/journal.pone.0049888 . 3501461. 2012PLoSO...749888A . free .
4. Wilson W et al. . Genomic exploration of individual giant ocean viruses. . The ISME Journal . 11 . 8 . 1736–1745 . 2017 . 10.1038/ismej.2017.61 . 28498373 . 5520044 .
5. Vercammen D, van de Cotte B, De Jaeger G, etal . Type II metacaspases Atmc4 and Atmc9 of Arabidopsis thaliana cleave substrates after arginine and lysine . J Biol Chem . 279 . 44 . 45329–36 . Oct 2004 . 15326173 . 10.1074/jbc.M406329200 . free .
6. Nedelcu AM, Miles IH, Fagir AM, Karol K . Adaptive eukaryote-to-eukaryote lateral gene transfer: stress-related genes of algal origin in the closest unicellular relatives of animals . J Evol Biol . 21. 6. 1852–60. Aug 2008 . 18717747 . 10.1111/j.1420-9101.2008.01605.x . free .
7. Madeo F, Herker E, Maldener C, etal . A caspase-related protease regulates apoptosis in yeast . Molecular Cell . 9 . 4 . 911–7 . Apr 2002 . 11983181 . 10.1016/S1097-2765(02)00501-4. free .
8. Bozhkov PV, Suarez MF, Filonova LH, etal . Cysteine protease mcII-Pa executes programmed cell death during plant embryogenesis . Proc Natl Acad Sci U S A . 102 . 40 . 14463–8 . Oct 2005 . 16183741 . 1242326 . 10.1073/pnas.0506948102 . 2005PNAS..10214463B . free .
9. Khan MA, Chock PB, Stadtman ER . Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae . Proc Natl Acad Sci U S A . 102 . 48 . 17326–31 . Nov 2005 . 16301538 . 1287485 . 10.1073/pnas.0508120102 . 2005PNAS..10217326K . free .