| Peptidase_S26 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Peptidase_S26 | ||||||||
| Pfam | PF10502 | ||||||||
| Pfam clan | CL0299 | ||||||||
| InterPro | IPR019533 | ||||||||
| MEROPS | S26 | ||||||||
| OPM superfamily | 137 | ||||||||
| OPM protein | 1t7d | ||||||||
| Membranome | 323 | ||||||||
| |||||||||
| Signal peptidase complex subunit 3 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | SP3 | ||||||||
| Pfam | PF04573 | ||||||||
| InterPro | IPR007653 | ||||||||
| Membranome | 369 | ||||||||
| |||||||||
| Signal peptidase I | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 3.4.21.89 | ||||||||
| CAS no. | 65979-36-4 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
| Signal peptidase II | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 3.4.23.36 | ||||||||
| CAS no. | 171715-14-3 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
Signal peptidases are enzymes that convert secretory and some membrane proteins to their mature or pro forms by cleaving their signal peptides from their N-termini.
Signal peptidases were initially observed in endoplasmic reticulum (ER)-derived membrane fractions isolated from mouse myeloma cells.[1] The key observation by César Milstein and colleagues was that immunoglobulin light chains were produced in a higher molecular weight form, which became processed by the ER membrane fraction. This finding was directly followed by the discovery of the translocation machinery.[2] Signal peptidases are also found in prokaryotes as well as the protein import machinery of mitochondria and chloroplasts.[3]
All signal peptidases described so far are serine proteases. The active site that endoproteolytically cleaves signal peptides from translocated precursor proteins is located at the extracytoplasmic site of the membrane. The eukaryotic signal peptidase is an integral membrane protein complex. The first subunit, which was identified by yeast genetics is Sec11, a 17 kDa membrane protein that is associated with three subunits termed Spc3p (21 kDa), Spc2p (18 kDa) and Spc1p (11 kDa). Sec11 is the only essential factor for signal peptide processing as can be deduced from a growth defect upon its deletion.[4] The functional signal peptidase complex was first purified from a canine ER membrane fraction.[5] The five mammalian subunits, originally named according to their molecular weight are referred to as SPCS1 (SPC12), SEC11A (SPC18), SEC11C (SPC21), SPCS3 (SPC22/23) and SPCS2 (SPC25). These subunits assemble into two distinct paralogous complexes differing in their catalytic subunit SEC11A and SEC11C, respectively, which exhibit largely identical structures.[6] The SPC structure suggests that the enzyme has a transmembrane domain that is only accessible to signal peptides with their characteristically short helical segment.
References
- ↑ Milstein C, Brownlee GG, Harrison TM, Mathews MB (September 1972). "A possible precursor of immunoglobulin light chains". Nature. 239 (91): 117–120. doi:10.1038/newbio239117a0. PMID 4507519.
- ↑ Blobel G, Dobberstein B (December 1975). "Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma". The Journal of Cell Biology. 67 (3): 835–851. doi:10.1083/jcb.67.3.835. PMC 2111658. PMID 811671.
- ↑ Paetzel M, Karla A, Strynadka NC, Dalbey RE (December 2002). "Signal peptidases". Chemical Reviews. 102 (12): 4549–4580. doi:10.1021/cr010166y. PMID 12475201.
- ↑ Böhni PC, Deshaies RJ, Schekman RW (April 1988). "SEC11 is required for signal peptide processing and yeast cell growth". The Journal of Cell Biology. 106 (4): 1035–1042. doi:10.1083/jcb.106.4.1035. PMC 2115025. PMID 3283143.
- ↑ Evans EA, Gilmore R, Blobel G (February 1986). "Purification of microsomal signal peptidase as a complex". Proceedings of the National Academy of Sciences of the United States of America. 83 (3): 581–585. Bibcode:1986PNAS...83..581E. doi:10.1073/pnas.83.3.581. PMC 322907. PMID 3511473.
- ↑ Liaci AM, Steigenberger B, Telles de Souza PC, Tamara S, Gröllers-Mulderij M, Ogrissek P, et al. (October 2021). "Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage". Molecular Cell. 81 (19): 3934–3948.e11. doi:10.1016/j.molcel.2021.07.031. hdl:1874/412779. PMID 34388369. S2CID 237010364.
External links
- signal+peptidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Further reading
- Calo D, Eichler J (March 2011). "Crossing the membrane in Archaea, the third domain of life". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1808 (3): 885–891. doi:10.1016/j.bbamem.2010.03.020. PMID 20347718.