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.
Structure of the human signal peptidase complex (PDB code 7P2P)
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.
Referencesedit
^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. PMC2111658. 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. PMC2115025. 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. PMC322907. 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.
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.
signal, peptidase, also, signal, peptide, peptidase, enzymes, that, convert, secretory, some, membrane, proteins, their, mature, forms, cleaving, their, signal, peptides, from, their, termini, structure, human, signal, peptidase, complex, code, 7p2p, peptidase. See also Signal peptide peptidase 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 Structure of the human signal peptidase complex PDB code 7P2P Peptidase S26IdentifiersSymbolPeptidase S26PfamPF10502Pfam clanCL0299InterProIPR019533MEROPSS26OPM superfamily137OPM protein1t7dMembranome323Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summarySignal peptidase complex subunit 3IdentifiersSymbolSP3PfamPF04573InterProIPR007653Membranome369Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summarySignal peptidase IIdentifiersEC no 3 4 21 89CAS no 65979 36 4DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteinsSignal peptidase IIIdentifiersEC no 3 4 23 36CAS no 171715 14 3DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteinsSignal peptidases were initially observed in endoplasmic reticulum ER derived membrane fractions isolated from mouse myeloma cells 1 The key observation by Cesar 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 edit 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 Bohni 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 Grollers 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 editsignal peptidase at the U S National Library of Medicine Medical Subject Headings MeSH Further reading editCalo 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 Portal nbsp Biology Retrieved from https en wikipedia org w index php title Signal peptidase amp oldid 1172360815, wikipedia, wiki, book, books, library,
