Signal recognition particle

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signal recognition particle 9kDa
Identifiers
Symbol SRP9
Entrez 6726
HUGO 11304
OMIM 600707
RefSeq NM_003133
UniProt P49458
Other data
Locus Chr. 1 q42.12
signal recognition particle 19kDa
Identifiers
Symbol SRP19
Entrez 6728
HUGO 11300
OMIM 182175
RefSeq NM_003135
UniProt P09132
Other data
Locus Chr. 5 q21-q22
signal recognition particle 54kDa
Identifiers
Symbol SRP54
Entrez 6729
HUGO 11301
OMIM 604857
RefSeq NM_003136
UniProt P61011
Other data
Locus Chr. 14 q13.2
signal recognition particle 68kDa
Identifiers
Symbol SRP68
Entrez 6730
HUGO 11302
OMIM 604858
RefSeq NM_014230
UniProt Q9UHB9
Other data
Locus Chr. 17 q25.1
signal recognition particle 72kDa
Identifiers
Symbol SRP72
Entrez 6731
HUGO 11303
OMIM 602122
RefSeq NM_006947
UniProt O76094
Other data
Locus Chr. 4 q11

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.

History[edit]

The function of SRP was discovered by the study of processed and unprocessed immunoglobulin light chains,[1] newly synthesized proteins in eukaryotes carry N-terminal hydrophobic signal sequences, which are bound by SRP when they emerge from the ribosome.[2][3]

Mechanism[edit]

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.[4] SRP then targets this entire complex (the ribosome-nascent chain complex) to the protein-conducting channel, also known as the translocon, in the ER (Endoplasmic reticulum) membrane. This occurs via the interaction and docking of SRP with its cognate SRP receptor[5] 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)[6] and the SRP protein SRP54 (known as Ffh in bacteria).[7] 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.[8][9]

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.[10][11] The SRP-SRP receptor complex dissociates via GTP hydrolysis and the cycle of SRP-mediated protein translocation continues.[12]

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.

The composition of SRP[edit]

Despite SRP function being analogous in all organisms, its composition varies greatly. The eukaryotic SRP is composed of six distinct polypeptides bound to an RNA molecule (the 7SL RNA), with GTPase activity. The components of the complex are:

  • SRP9
  • SRP14
  • SRP19
  • SRP54
  • SRP68
  • SRP72
  • SRP RNA

The prokaryotic SRP is composed of one polypeptide bound to an RNA molecule (the 4.5S RNA), with GTPase activity. The components of the complex are:

  • Ffh
  • 4.5S RNA

Ffh is the structural and functional homolog of the SRP54 protein in eukaryotes. The 4.5S RNA shares sequence and structural homology with one domain of the larger 7S RNA.

Crystallographic structures of representative SRPs
SRP19-7S.S SRP RNA complex from M. jannaschii[13] 
S-domain of human SRP[14] 

Autoantibodies[edit]

Anti-signal recognition particle antibodies are mainly associated with, but are not very specific for, polymyositis.[15] For individuals with polymyositis, the presence of anti-SRP antibodies are associated with more prominent muscle weakness and atrophy.[15]

See also[edit]

References[edit]

  1. ^ Milstein C, Brownlee GG, Harrison TM, Mathews MB (September 1972). "A possible precursor of immunoglobulin light chains". Nature: New Biology 239 (91): 117–20. PMID 4507519. 
  2. ^ Walter P, Ibrahimi I, Blobel G (November 1981). "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. doi:10.1083/jcb.91.2.545. PMC 2111968. PMID 7309795. 
  3. ^ Blobel G, Dobberstein B (December 1975). "Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribsomes of murine myeloma". The Journal of Cell Biology 67 (3): 835–51. doi:10.1083/jcb.67.3.835. PMC 2111658. PMID 811671. 
  4. ^ Walter P, Blobel G (December 1983). "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. doi:10.1083/jcb.97.6.1693. PMC 2112735. PMID 6196367. 
  5. ^ Gilmore R, Blobel G, Walter P (November 1982). "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. doi:10.1083/jcb.95.2.463. PMC 2112970. PMID 6292235. 
  6. ^ Rapiejko PJ, Gilmore R (May 1992). "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. doi:10.1083/jcb.117.3.493. PMC 2289435. PMID 1315314. 
  7. ^ Freymann DM, Keenan RJ, Stroud RM, Walter P (January 1997). "Structure of the conserved GTPase domain of the signal recognition particle". Nature 385 (6614): 361–4. doi:10.1038/385361a0. PMID 9002524. 
  8. ^ 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. doi:10.1038/366351a0. PMID 8247130. 
  9. ^ 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. PMID 19558326. 
  10. ^ Lütcke H (March 1995). "Signal recognition particle (SRP), a ubiquitous initiator of protein translocation". European Journal of Biochemistry / FEBS 228 (3): 531–50. doi:10.1111/j.1432-1033.1995.0531m.x. PMID 7737147. 
  11. ^ Luirink J, Sinning I (November 2004). "SRP-mediated protein targeting: structure and function revisited". Biochimica et Biophysica Acta 1694 (1-3): 17–35. doi:10.1016/j.bbamcr.2004.03.013. PMID 15546655. 
  12. ^ Shan SO, Walter P (February 2005). "Co-translational protein targeting by the signal recognition particle". FEBS Letters 579 (4): 921–6. doi:10.1016/j.febslet.2004.11.049. PMID 15680975. 
  13. ^ Hainzl T, Huang S, Sauer-Eriksson AE (2002). "Structure of the SRP19 RNA complex and implications for signal recognition particle assembly.". Nature 417 (6890): 767–71. doi:10.1038/nature00768. PMID 12050674. 
  14. ^ Kuglstatter A, Oubridge C, Nagai K (2002). "Induced structural changes of 7SL RNA during the assembly of human signal recognition particle.". Nat Struct Biol 9 (10): 740–4. doi:10.1038/nsb843. PMID 12244299. 
  15. ^ a b Kao, A. H.; Lacomis, D.; Lucas, M.; Fertig, N.; Oddis, C. V. (2004). "Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy". Arthritis & Rheumatism 50 (1): 209–215. doi:10.1002/art.11484. PMID 14730618.  edit

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