signal peptidase

{{see also|Signal peptide peptidase}}

File:SignalPeptidaseComplex.jpg

{{Infobox protein family

| Symbol = Peptidase_S26

| Name = Peptidase_S26

| image =

| width =

| caption =

| Pfam = PF10502

| Pfam_clan = CL0299

| InterPro = IPR019533

| SMART =

| PROSITE =

| MEROPS = S26

| SCOP =

| TCDB =

| OPM family = 137

| OPM protein = 1t7d

| CAZy =

| CDD =

| Membranome superfamily = 323

}}

{{Infobox protein family

| Symbol = SP3

| Name = Signal peptidase complex subunit 3

| image =

| width =

| caption =

| Pfam = PF04573

| Pfam_clan =

| InterPro = IPR007653

| SMART =

| PROSITE =

| MEROPS =

| SCOP =

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

| Membranome superfamily = 369

}}

{{infobox enzyme

| Name = Signal peptidase I

| EC_number = 3.4.21.89

| CAS_number = 65979-36-4

| GO_code = 0009004

| image =

| width =

| caption =

}}

{{infobox enzyme

| Name = Signal peptidase II

| EC_number = 3.4.23.36

| CAS_number = 171715-14-3

| GO_code = 0009005

| image =

| width =

| caption =

}}

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.{{cite journal | vauthors = Milstein C, Brownlee GG, Harrison TM, Mathews MB | title = A possible precursor of immunoglobulin light chains | journal = Nature | volume = 239 | issue = 91 | pages = 117–120 | date = September 1972 | pmid = 4507519 | doi = 10.1038/newbio239117a0 }} 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.{{cite journal | vauthors = Blobel G, Dobberstein B | title = Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma | journal = The Journal of Cell Biology | volume = 67 | issue = 3 | pages = 835–851 | date = December 1975 | pmid = 811671 | pmc = 2111658 | doi = 10.1083/jcb.67.3.835 }} Signal peptidases are also found in prokaryotes as well as the protein import machinery of mitochondria and chloroplasts.{{cite journal | vauthors = Paetzel M, Karla A, Strynadka NC, Dalbey RE | title = Signal peptidases | journal = Chemical Reviews | volume = 102 | issue = 12 | pages = 4549–4580 | date = December 2002 | pmid = 12475201 | doi = 10.1021/cr010166y }}

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.{{cite journal | vauthors = Böhni PC, Deshaies RJ, Schekman RW | title = SEC11 is required for signal peptide processing and yeast cell growth | journal = The Journal of Cell Biology | volume = 106 | issue = 4 | pages = 1035–1042 | date = April 1988 | pmid = 3283143 | pmc = 2115025 | doi = 10.1083/jcb.106.4.1035 }} The functional signal peptidase complex was first purified from a canine ER membrane fraction.{{cite journal | vauthors = Evans EA, Gilmore R, Blobel G | title = Purification of microsomal signal peptidase as a complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 3 | pages = 581–585 | date = February 1986 | pmid = 3511473 | pmc = 322907 | doi = 10.1073/pnas.83.3.581 | doi-access = free | bibcode = 1986PNAS...83..581E }} 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.{{cite journal | vauthors = Liaci AM, Steigenberger B, Telles de Souza PC, Tamara S, Gröllers-Mulderij M, Ogrissek P, Marrink SJ, Scheltema RA, Förster F | display-authors = 6 | title = Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage | journal = Molecular Cell | volume = 81 | issue = 19 | pages = 3934–3948.e11 | date = October 2021 | pmid = 34388369 | doi = 10.1016/j.molcel.2021.07.031 | hdl = 1874/412779 | s2cid = 237010364 | hdl-access = free }} The SPC structure suggests that the enzyme has a transmembrane domain that is only accessible to signal peptides with their characteristically short helical segment.