Signal peptide peptidase

Signal peptide peptidase

The Signal Peptide Peptidase (SPP) and its homologs (SPPL2a/b/c, SPPL3) are a class of transmembrane aspartyl proteases with the conserved motives YD ... GxGD ...PALL. Their sequences are highly conserved in different vertebrate species. Their substrates are Type II transmembrane proteins. [cite journal |author=Weihofen A, Binns K, Lemberg MK, Ashman K, Martoglio B |title=Identification of signal peptide peptidase, a presenilin-type aspartic protease |journal=Science |volume=296 |issue=5576 |pages=2215–8 |year=2002 |pmid=12077416 |doi=10.1126/science.1070925]

Physiologically SPP processes signal peptides of HLA preproteins. A 9 AS cleavage fragment is then presented on HLA-E receptors and modulates the activity of natural killer cells. [cite journal |author=Lemberg MK, Bland FA, Weihofen A, Braud VM, Martoglio B |title=Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes |journal=J. Immunol. |volume=167 |issue=11 |pages=6441–6 |year=2001 |pmid=11714810 |doi=]

SPP also plays a pathophysiolocigal role; it cleaves the core protein of Hepatitis C virus and thus influences the reproduction rate of HCV. [cite journal |author=Okamoto K, Moriishi K, Miyamura T, Matsuura Y |title=Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein |journal=J. Virol. |volume=78 |issue=12 |pages=6370–80 |year=2004 |pmid=15163730 |doi=10.1128/JVI.78.12.6370-6380.2004]

SPPL2a/b promotes the intramembrane cleavage of TNFα in activated dendritic cells and might play an immunomodulatory role. [cite journal |author=Friedmann E, Hauben E, Maylandt K, "et al" |title=SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production |journal=Nat. Cell Biol. |volume=8 |issue=8 |pages=843–8 |year=2006 |pmid=16829952 |doi=10.1038/ncb1440] [cite journal |author=Fluhrer R, Grammer G, Israel L, "et al" |title=A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b |journal=Nat. Cell Biol. |volume=8 |issue=8 |pages=894–6 |year=2006 |pmid=16829951 |doi=10.1038/ncb1450]

References

Further reading

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External links

* - Calculated spatial position of type 1 signal peptidase in membrane
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