Biology:Signal recognition particle

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Short description: Protein-RNA complex
signal recognition particle 9kDa
Identifiers
SymbolSRP9
NCBI gene6726
HGNC11304
OMIM600707
RefSeqNM_003133
UniProtP49458
Other data
LocusChr. 1 q42.12
signal recognition particle 14kDa
Identifiers
SymbolSRP14
NCBI gene6727
HGNC11299
OMIM600708
RefSeqNM_003134
UniProtP37108
Other data
LocusChr. 15 q22
signal recognition particle 19kDa
Identifiers
SymbolSRP19
NCBI gene6728
HGNC11300
OMIM182175
RefSeqNM_003135
UniProtP09132
Other data
LocusChr. 5 q21-q22
signal recognition particle 54kDa
Identifiers
SymbolSRP54
NCBI gene6729
HGNC11301
OMIM604857
RefSeqNM_003136
UniProtP61011
Other data
LocusChr. 14 q13.2
signal recognition particle 68kDa
Identifiers
SymbolSRP68
NCBI gene6730
HGNC11302
OMIM604858
RefSeqNM_014230
UniProtQ9UHB9
Other data
LocusChr. 17 q25.1
signal recognition particle 72kDa
Identifiers
SymbolSRP72
NCBI gene6731
HGNC11303
OMIM602122
RefSeqNM_006947
UniProtO76094
Other data
LocusChr. 4 q11
Signal recognition particle protein
Identifiers
OrganismEscherichia coli (strain K12)
Symbolffh
Alt. symbolsp48, Srp54
UniProtP0AGD7

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.[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.

SRP Subunits in three domains of life
Eukaryote Archaea Bacteria
SRP9
SRP14		 No No
SRP19 Yes No
SRP54 Yes Ffh
SRP68
SRP72		 No No
7SL RNA Yes 6SL​/4.5SL RNA
Crystallographic structures of representative SRPs

Autoantibodies and disease

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]

See also

References

  1. ↑ 1.0 1.1 "Chapter 7 - RNA-Processing Dysfunction in Spinal Muscular Atrophy" (in en). Spinal Muscular Atrophy. Academic Press. 2017-01-01. pp. 113–131. doi:10.1016/b978-0-12-803685-3.00007-0. ISBN 978-0-12-803685-3. 
  2. ↑ "A possible precursor of immunoglobulin light chains". Nature 239 (91): 117–20. September 1972. doi:10.1038/newbio239117a0. PMID 4507519. 
  3. ↑ "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. doi:10.1083/jcb.91.2.545. PMID 7309795. 
  4. ↑ "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. doi:10.1083/jcb.67.3.835. PMID 811671. 
  5. ↑ "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. doi:10.1083/jcb.97.6.1693. PMID 6196367. 
  6. ↑ "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. doi:10.1083/jcb.95.2.463. PMID 6292235. 
  7. ↑ "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. doi:10.1083/jcb.117.3.493. PMID 1315314. 
  8. ↑ "Structure of the conserved GTPase domain of the signal recognition particle". Nature 385 (6614): 361–4. January 1997. doi:10.1038/385361a0. PMID 9002524. Bibcode: 1997Natur.385..361F. 
  9. ↑ "GTP binding and hydrolysis by the signal recognition particle during initiation of protein translocation". Nature 366 (6453): 351–4. November 1993. doi:10.1038/366351a0. PMID 8247130. Bibcode: 1993Natur.366..351M. 
  10. ↑ "Protein targeting by the signal recognition particle". Biological Chemistry 390 (8): 775–82. August 2009. doi:10.1515/BC.2009.102. PMID 19558326. 
  11. ↑ "Signal recognition particle (SRP), a ubiquitous initiator of protein translocation". European Journal of Biochemistry 228 (3): 531–50. March 1995. doi:10.1111/j.1432-1033.1995.0531m.x. PMID 7737147. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1995&volume=228&issue=3&spage=531. [|permanent dead link|dead link}}]
  12. ↑ "SRP-mediated protein targeting: structure and function revisited". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1694 (1–3): 17–35. November 2004. doi:10.1016/j.bbamcr.2004.03.013. PMID 15546655. 
  13. ↑ "Co-translational protein targeting by the signal recognition particle". FEBS Letters 579 (4): 921–6. February 2005. doi:10.1016/j.febslet.2004.11.049. PMID 15680975. 
  14. ↑ "Structure of the SRP19 RNA complex and implications for signal recognition particle assembly". Nature 417 (6890): 767–71. June 2002. doi:10.1038/nature00768. PMID 12050674. Bibcode: 2002Natur.417..767H. 
  15. ↑ "Induced structural changes of 7SL RNA during the assembly of human signal recognition particle". Nature Structural Biology 9 (10): 740–4. October 2002. doi:10.1038/nsb843. PMID 12244299. 
  16. ↑ 16.0 16.1 "Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy". Arthritis and Rheumatism 50 (1): 209–15. January 2004. doi:10.1002/art.11484. PMID 14730618. 

Further reading

External links



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