Signal recognition particle explained
| signal recognition particle 9kDa |
| Hgncid: | 11304 |
| Symbol: | SRP9 |
| Entrezgene: | 6726 |
| Omim: | 600707 |
| Refseq: | NM_003133 |
| Uniprot: | P49458 |
| Chromosome: | 1 |
| Arm: | q |
| Band: | 42.12 |
| signal recognition particle 14kDa |
| Hgncid: | 11299 |
| Symbol: | SRP14 |
| Entrezgene: | 6727 |
| Omim: | 600708 |
| Refseq: | NM_003134 |
| Uniprot: | P37108 |
| Chromosome: | 15 |
| Arm: | q |
| Band: | 22 |
| signal recognition particle 19kDa |
| Hgncid: | 11300 |
| Symbol: | SRP19 |
| Entrezgene: | 6728 |
| Omim: | 182175 |
| Refseq: | NM_003135 |
| Uniprot: | P09132 |
| Chromosome: | 5 |
| Arm: | q |
| Band: | 21 |
| Locussupplementarydata: | -q22 |
| signal recognition particle 54kDa |
| Hgncid: | 11301 |
| Symbol: | SRP54 |
| Entrezgene: | 6729 |
| Omim: | 604857 |
| Refseq: | NM_003136 |
| Uniprot: | P61011 |
| Chromosome: | 14 |
| Arm: | q |
| Band: | 13.2 |
| signal recognition particle 68kDa |
| Hgncid: | 11302 |
| Symbol: | SRP68 |
| Entrezgene: | 6730 |
| Omim: | 604858 |
| Refseq: | NM_014230 |
| Uniprot: | Q9UHB9 |
| Chromosome: | 17 |
| Arm: | q |
| Band: | 25.1 |
| signal recognition particle 72kDa |
| Hgncid: | 11303 |
| Symbol: | SRP72 |
| Entrezgene: | 6731 |
| Omim: | 602122 |
| Refseq: | NM_006947 |
| Uniprot: | O76094 |
| Chromosome: | 4 |
| Arm: | q |
| Band: | 11 |
| Signal recognition particle protein |
| Symbol: | ffh |
| Organism: | Escherichia coli (strain K12) |
| Uniprot: | P0AGD7 |
| Altsymbols: | p48, Srp54 |
The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein (protein-RNA complex) that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes.[1]
History
The function of SRP was discovered by the study of processed and unprocessed secretory proteins, particularly immunoglobulin light chains;[2] and bovine preprolactin. Newly synthesized proteins in eukaryotes carry N-terminal hydrophobic signal sequences, which are bound by SRP when they emerge from the ribosome.[3] [4]
Mechanism
In eukaryotes, SRP binds to the signal sequence of a newly synthesized peptide as it emerges from the ribosome. This binding leads to the slowing of protein synthesis known as "elongation arrest", a conserved function of SRP that facilitates the coupling of the protein translation and the protein translocation processes.[5] SRP then targets this entire complex (the ribosome-nascent chain complex) to the protein-conducting channel, also known as the translocon, in the endoplasmic reticulum (ER) membrane. This occurs via the interaction and docking of SRP with its cognate SRP receptor[6] that is located in close proximity to the translocon.
In eukaryotes there are three domains between SRP and its receptor that function in guanosine triphosphate (GTP) binding and hydrolysis. These are located in two related subunits in the SRP receptor (SRα and SRβ)[7] and the SRP protein SRP54 (known as Ffh in bacteria).[8] The coordinated binding of GTP by SRP and the SRP receptor has been shown to be a prerequisite for the successful targeting of SRP to the SRP receptor.[9] [10]
Upon docking, the nascent peptide chain is inserted into the translocon channel where it enters into the ER. Protein synthesis resumes as SRP is released from the ribosome.[11] [12] The SRP-SRP receptor complex dissociates via GTP hydrolysis and the cycle of SRP-mediated protein translocation continues.[13]
Once inside the ER, the signal sequence is cleaved from the core protein by signal peptidase. Signal sequences are therefore not a part of mature proteins.
Composition and evolution
Despite SRP function being analogous in all organisms, its composition varies greatly. The SRP54-SRP RNA core with GTPase activity is shared in all cellular life, but some subunit polypeptides are specific to eukaryotes.
Autoantibodies and disease
Anti-signal recognition particle antibodies are mainly associated with, but are not very specific for, polymyositis. For individuals with polymyositis, the presence of anti-SRP antibodies are associated with more prominent muscle weakness and atrophy.[14]
See also
Further reading
- Wild K, Becker MM, Kempf G, Sinning I . Structure, dynamics and interactions of large SRP variants . Biological Chemistry . 401 . 1 . 63–80 . December 2019 . 31408431 . 10.1515/hsz-2019-0282 . free .
- Faoro C, Ataide SF . Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components . Frontiers in Molecular Biosciences . 8 . 679584 . 25 May 2021 . 34113652 . 10.3389/fmolb.2021.679584 . 8185352 . free .
External links
Notes and References
- Book: Tisdale S, Pellizzoni L . Chapter 7 - RNA-Processing Dysfunction in Spinal Muscular Atrophy. 2017-01-01 . Spinal Muscular Atrophy. 113–131. Sumner CJ, Paushkin S, KO CP . Academic Press. en. 10.1016/b978-0-12-803685-3.00007-0. 978-0-12-803685-3.
- Milstein C, Brownlee GG, Harrison TM, Mathews MB . A possible precursor of immunoglobulin light chains . Nature . 239 . 91 . 117–20 . September 1972 . 4507519 . 10.1038/newbio239117a0 .
- Walter P, Ibrahimi I, Blobel G . Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein . The Journal of Cell Biology . 91 . 2 Pt 1 . 545–50 . November 1981 . 7309795 . 2111968 . 10.1083/jcb.91.2.545 .
- Blobel G, Dobberstein B . 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 . 835–51 . December 1975 . 811671 . 2111658 . 10.1083/jcb.67.3.835 .
- Walter P, Blobel G . Subcellular distribution of signal recognition particle and 7SL-RNA determined with polypeptide-specific antibodies and complementary DNA probe . The Journal of Cell Biology . 97 . 6 . 1693–9 . December 1983 . 6196367 . 2112735 . 10.1083/jcb.97.6.1693 .
- Gilmore R, Blobel G, Walter P . Protein translocation across the endoplasmic reticulum. I. Detection in the microsomal membrane of a receptor for the signal recognition particle . The Journal of Cell Biology . 95 . 2 Pt 1 . 463–9 . November 1982 . 6292235 . 2112970 . 10.1083/jcb.95.2.463 .
- Rapiejko PJ, Gilmore R . Protein translocation across the ER requires a functional GTP binding site in the alpha subunit of the signal recognition particle receptor . The Journal of Cell Biology . 117 . 3 . 493–503 . May 1992 . 1315314 . 2289435 . 10.1083/jcb.117.3.493 .
- Freymann DM, Keenan RJ, Stroud RM, Walter P . Structure of the conserved GTPase domain of the signal recognition particle . Nature . 385 . 6614 . 361–4 . January 1997 . 9002524 . 10.1038/385361a0 . 1997Natur.385..361F . 4238766 .
- Miller JD, Wilhelm H, Gierasch L, Gilmore R, Walter P . GTP binding and hydrolysis by the signal recognition particle during initiation of protein translocation . Nature . 366 . 6453 . 351–4 . November 1993 . 8247130 . 10.1038/366351a0 . 1993Natur.366..351M . 4326097 .
- Grudnik P, Bange G, Sinning I . Protein targeting by the signal recognition particle . Biological Chemistry . 390 . 8 . 775–82 . August 2009 . 19558326 . 10.1515/BC.2009.102 . 36611716 .
- Lütcke H . Signal recognition particle (SRP), a ubiquitous initiator of protein translocation . European Journal of Biochemistry . 228 . 3 . 531–50 . March 1995 . 7737147 . 10.1111/j.1432-1033.1995.0531m.x .
- Luirink J, Sinning I . SRP-mediated protein targeting: structure and function revisited . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1694 . 1–3 . 17–35 . November 2004 . 15546655 . 10.1016/j.bbamcr.2004.03.013 . free .
- Shan SO, Walter P . Co-translational protein targeting by the signal recognition particle . FEBS Letters . 579 . 4 . 921–6 . February 2005 . 15680975 . 10.1016/j.febslet.2004.11.049 . 46046514 .
- Kao AH, Lacomis D, Lucas M, Fertig N, Oddis CV . Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy . Arthritis and Rheumatism . 50 . 1 . 209–15 . January 2004 . 14730618 . 10.1002/art.11484 .
