This article is missing information about overall structure (as context for "S domain" pics and for mechanism description); rough structure and function of binding proteins. Please expand the article to include this information. Further details may exist on the talk page.(October 2021)
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.[1] 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.
Anti-signal recognition particle antibodies are mainly associated with, but are not very specific for, polymyositis.[16] For individuals with polymyositis, the presence of anti-SRP antibodies are associated with more prominent muscle weakness and atrophy.[16]
^Miller JD, Wilhelm H, Gierasch L, Gilmore R, Walter P (November 1993). "GTP binding and hydrolysis by the signal recognition particle during initiation of protein translocation". Nature. 366 (6453): 351–4. Bibcode:1993Natur.366..351M. doi:10.1038/366351a0. PMID8247130. S2CID4326097.
^Grudnik P, Bange G, Sinning I (August 2009). "Protein targeting by the signal recognition particle". Biological Chemistry. 390 (8): 775–82. doi:10.1515/BC.2009.102. PMID19558326. S2CID36611716.
^Kuglstatter A, Oubridge C, Nagai K (October 2002). "Induced structural changes of 7SL RNA during the assembly of human signal recognition particle". Nature Structural Biology. 9 (10): 740–4. doi:10.1038/nsb843. PMID12244299. S2CID9543041.
^ abKao AH, Lacomis D, Lucas M, Fertig N, Oddis CV (January 2004). "Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy". Arthritis and Rheumatism. 50 (1): 209–15. doi:10.1002/art.11484. PMID14730618.
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
![SRP19-7S.S SRP RNA complex from M. jannaschii[14]](File:PDB_1lng_EBI.jpg)
![S-domain of human SRP[15]](File:PDB_1mfq_EBI.jpg)