signal recognition particle

The function of SRP was discovered by the study of processed and unprocessed secretory proteins, particularly immunoglobulin light chains;{{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 = 117–20 | date = September 1972 | pmid = 4507519 | doi = 10.1038/newbio239117a0 }} 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.{{cite journal | vauthors = Walter P, Ibrahimi I, Blobel G | title = Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein | journal = The Journal of Cell Biology | volume = 91 | issue = 2 Pt 1 | pages = 545–50 | date = November 1981 | pmid = 7309795 | pmc = 2111968 | doi = 10.1083/jcb.91.2.545 }}{{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 = 835–51 | date = December 1975 | pmid = 811671 | pmc = 2111658 | doi = 10.1083/jcb.67.3.835 }}

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.{{cite journal | vauthors = Walter P, Blobel G | title = Subcellular distribution of signal recognition particle and 7SL-RNA determined with polypeptide-specific antibodies and complementary DNA probe | journal = The Journal of Cell Biology | volume = 97 | issue = 6 | pages = 1693–9 | date = December 1983 | pmid = 6196367 | pmc = 2112735 | doi = 10.1083/jcb.97.6.1693 }} 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{{cite journal | vauthors = Gilmore R, Blobel G, Walter P | title = Protein translocation across the endoplasmic reticulum. I. Detection in the microsomal membrane of a receptor for the signal recognition particle | journal = The Journal of Cell Biology | volume = 95 | issue = 2 Pt 1 | pages = 463–9 | date = November 1982 | pmid = 6292235 | pmc = 2112970 | doi = 10.1083/jcb.95.2.463 }} 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){{cite journal | vauthors = Rapiejko PJ, Gilmore R | title = Protein translocation across the ER requires a functional GTP binding site in the alpha subunit of the signal recognition particle receptor | journal = The Journal of Cell Biology | volume = 117 | issue = 3 | pages = 493–503 | date = May 1992 | pmid = 1315314 | pmc = 2289435 | doi = 10.1083/jcb.117.3.493 }} and the SRP protein SRP54 (known as Ffh in bacteria).{{cite journal | vauthors = Freymann DM, Keenan RJ, Stroud RM, Walter P | title = Structure of the conserved GTPase domain of the signal recognition particle | journal = Nature | volume = 385 | issue = 6614 | pages = 361–4 | date = January 1997 | pmid = 9002524 | doi = 10.1038/385361a0 | bibcode = 1997Natur.385..361F | s2cid = 4238766 }} 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.{{cite journal | vauthors = Miller JD, Wilhelm H, Gierasch L, Gilmore R, Walter P | title = GTP binding and hydrolysis by the signal recognition particle during initiation of protein translocation | journal = Nature | volume = 366 | issue = 6453 | pages = 351–4 | date = November 1993 | pmid = 8247130 | doi = 10.1038/366351a0 | bibcode = 1993Natur.366..351M | s2cid = 4326097 }}{{cite journal | vauthors = Grudnik P, Bange G, Sinning I | title = Protein targeting by the signal recognition particle | journal = Biological Chemistry | volume = 390 | issue = 8 | pages = 775–82 | date = August 2009 | pmid = 19558326 | doi = 10.1515/BC.2009.102 | s2cid = 36611716 }}

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.{{cite journal | vauthors = Lütcke H | title = Signal recognition particle (SRP), a ubiquitous initiator of protein translocation | journal = European Journal of Biochemistry | volume = 228 | issue = 3 | pages = 531–50 | date = March 1995 | pmid = 7737147 | doi = 10.1111/j.1432-1033.1995.0531m.x | url = http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1995&volume=228&issue=3&spage=531 | archive-url = https://archive.today/20130105065231/http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1995&volume=228&issue=3&spage=531 | url-status = dead | archive-date = January 5, 2013 | url-access = subscription }}{{cite journal | vauthors = Luirink J, Sinning I | title = SRP-mediated protein targeting: structure and function revisited | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1694 | issue = 1–3 | pages = 17–35 | date = November 2004 | pmid = 15546655 | doi = 10.1016/j.bbamcr.2004.03.013 | doi-access = free }} The SRP-SRP receptor complex dissociates via GTP hydrolysis and the cycle of SRP-mediated protein translocation continues.{{cite journal | vauthors = Shan SO, Walter P | title = Co-translational protein targeting by the signal recognition particle | journal = FEBS Letters | volume = 579 | issue = 4 | pages = 921–6 | date = February 2005 | pmid = 15680975 | doi = 10.1016/j.febslet.2004.11.049 | s2cid = 46046514 | doi-access = }}

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.

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.

{{Gallery

|title=Crystallographic structures of representative SRPs

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|File:PDB 1lng EBI.jpg|SRP19-7S.S SRP RNA complex from M. jannaschii{{cite journal | vauthors = Hainzl T, Huang S, Sauer-Eriksson AE | title = Structure of the SRP19 RNA complex and implications for signal recognition particle assembly | journal = Nature | volume = 417 | issue = 6890 | pages = 767–71 | date = June 2002 | pmid = 12050674 | doi = 10.1038/nature00768 | bibcode = 2002Natur.417..767H | s2cid = 2509475 }}

|File:PDB 1mfq EBI.jpg| S-domain of human SRP{{cite journal | vauthors = Kuglstatter A, Oubridge C, Nagai K | title = Induced structural changes of 7SL RNA during the assembly of human signal recognition particle | journal = Nature Structural Biology | volume = 9 | issue = 10 | pages = 740–4 | date = October 2002 | pmid = 12244299 | doi = 10.1038/nsb843 | s2cid = 9543041 }}

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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.{{cite journal | vauthors = Kao AH, Lacomis D, Lucas M, Fertig N, Oddis CV | title = Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy | journal = Arthritis and Rheumatism | volume = 50 | issue = 1 | pages = 209–15 | date = January 2004 | pmid = 14730618 | doi = 10.1002/art.11484 | doi-access = }}

• Signal recognition particle RNA

{{Reflist|30em}}

{{refbegin}}

• {{cite journal | vauthors = Wild K, Becker MM, Kempf G, Sinning I | title = Structure, dynamics and interactions of large SRP variants | journal = Biological Chemistry | volume = 401 | issue = 1 | pages = 63–80 | date = December 2019 | pmid = 31408431 | doi = 10.1515/hsz-2019-0282 | doi-access = free }}
• {{cite journal | vauthors = Faoro C, Ataide SF | title = Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components | journal = Frontiers in Molecular Biosciences | volume = 8 | pages = 679584 | date = 25 May 2021 | pmid = 34113652 | doi = 10.3389/fmolb.2021.679584 | pmc = 8185352 | doi-access = free }}

{{refend}}

• {{MeshName|Signal+Recognition+Particle}}
• [http://rnp.uthscsa.edu/ Signal Recognition Particle Database]{{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}
• [http://www.dnatube.com/video/1227/Signal-Recognition-Particle www.dnaTube.com video showing an SRP in action]
• [http://www.dnatube.com/video/544/Signal-Recognition-Particle-SRP Another SRP video at www.dnaTube.com]
• [http://nobelprize.org/nobel_prizes/medicine/laureates/1999/index.html The Nobel Prize in Physiology or Medicine 1999], "for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell" to Günter Blobel, USA. Press Release, Illustrated Presentation, Presentation Speech

{{Ribonucleoproteins}}

Category:Cell signaling