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Gene Review

SRP54  -  signal recognition particle 54kDa

Homo sapiens

Synonyms: Signal recognition particle 54 kDa protein
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Disease relevance of SRP54

  • E. coli 4.5S RNA and P48 have been shown to be homologous to SRP7S RNA and SRP54, respectively [1].
  • In the current article, we have characterized the specificity of anti-SRP54 autoantibodies, which are highly characteristic of polymyositis patients, and investigated the effect of these autoantibodies on the SRP function in vitro [2].

High impact information on SRP54

  • During assembly of the SRP, binding of SRP19 precedes and promotes the association of SRP54 (refs 4, 5) [3].
  • Targeting is regulated by three GTPases, the 54K subunit of SRP (SRP54), and the alpha- and beta-subunits of the SRP receptor [4].
  • Here we use a complex of a ribosome with a nascent peptide chain, the SRP and its receptor, to investigate GTP binding to SRP54, and GTP hydrolysis [4].
  • Helix 6 acts as a splint for helix 8 and partially preorganizes the binding site for SRP54 in helix 8, thereby facilitating the binding of SRP54 in assembly [5].
  • By photo-crosslinking it has been shown that the signal sequence of preprolactin (PPL) only interacts with the methionine-rich (M) domain of the 54 kDa protein subunit (SRP54) of SRP [6].

Biological context of SRP54

  • Reduced protein-binding activities of these chimeras demonstrated a considerable overlap of regions required for SRP54 binding and assembly control [7].
  • To understand better how protein targeting occurs in the human system, the human SRP54 gene was cloned, sequenced, and the protein was expressed in bacteria and insect cells [8].
  • Alkylation of the N+G domain in intact SRP54 with N-ethyl maleimide (NEM), but not after cleavage with V8 protease, prevents the binding of a signal sequence to the M domain [6].
  • In higher eukaryotes, SRP biogenesis involves the sequential binding of SRP19 and SRP54 proteins to the S domain of 7S RNA [9].
  • SRP54 depletion elicited inhibition in growth and cytokinesis, suggesting that the SRP pathway is essential [10].

Anatomical context of SRP54

  • Protein SRP54 is an integral part of the mammalian signal recognition particle (SRP), a cytosolic ribonucleoprotein complex which associates with ribosomes and serves to recognize, bind, and transport proteins destined for the membrane or secretion [11].
  • Here we show that 54CP, a chloroplast homologue of the 54-kDa subunit of the mammalian signal recognition particle (SRP54), is essential for transit complex formation, is present in the complex, and is required for LHCP integration into the thylakoid membrane [12].
  • A chloroplast homologue of the signal recognition particle subunit SRP54 is involved in the posttranslational integration of a protein into thylakoid membranes [12].
  • The translocation of these proteins to the endoplasmic reticulum under SRP54 depletion suggests that an alternative pathway for protein translocation exists in trypanosomes [10].
  • The 54-kDa subunit SRP54 of the signal recognition particle in eukaryotic cells is responsible for the recognition of nascent proteins destined for secretion or membrane integration [13].

Associations of SRP54 with chemical compounds

  • The strongest effects on the binding activity of a purified polypeptide that corresponds to the methionine-rich domain of SRP54 (SRP54M) were caused by changes in helix 8 of the SRP RNA [14].
  • S. pombe SRP RNA and Srp54p co-sediment on a sucrose velocity gradient and coimmunoprecipitate, indicating that they reside in the same complex [15].

Physical interactions of SRP54

  • Hence, the crystal structure of the ternary complex suggests why SRP19 is necessary for the stable binding of SRP54 to the S domain RNA [16].
  • At the ER membrane, the binding of the signal recognition particle (SRP) to its receptor triggers the release of SRP54 from its bound signal sequence and the nascent polypeptide is transferred to the Sec61 translocon for insertion into, or translocation across, the ER membrane [2].

Regulatory relationships of SRP54


Other interactions of SRP54

  • The structure explains the role of SRP19 and provides a molecular framework for SRP54 binding and SRP assembly in Eukarya and Archaea [3].
  • The binding of SRP54 to the S domain of 7SL RNA is highly dependent on SRP19 [16].
  • The conservation of this sequence, in combination with the results of earlier genetic and biochemical studies of the SRP cycle, leads us to hypothesize that a component of the Srp68/72p heterodimer serves as the GDS for both Srp54p and SR alpha [18].
  • The transmembrane protein SR beta also contains a GTPase domain, but it is not closely related to those of SRP54 and SR alpha [17].

Analytical, diagnostic and therapeutic context of SRP54


  1. E. coli 4.5S RNA is part of a ribonucleoprotein particle that has properties related to signal recognition particle. Ribes, V., Römisch, K., Giner, A., Dobberstein, B., Tollervey, D. Cell (1990) [Pubmed]
  2. Human autoantibodies against the 54 kDa protein of the signal recognition particle block function at multiple stages. Römisch, K., Miller, F.W., Dobberstein, B., High, S. Arthritis Res. Ther. (2006) [Pubmed]
  3. Structure of the SRP19 RNA complex and implications for signal recognition particle assembly. Hainzl, T., Huang, S., Sauer-Eriksson, A.E. Nature (2002) [Pubmed]
  4. Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting. Bacher, G., Lütcke, H., Jungnickel, B., Rapoport, T.A., Dobberstein, B. Nature (1996) [Pubmed]
  5. Crystal structure of SRP19 in complex with the S domain of SRP RNA and its implication for the assembly of the signal recognition particle. Oubridge, C., Kuglstatter, A., Jovine, L., Nagai, K. Mol. Cell (2002) [Pubmed]
  6. The methionine-rich domain of the 54 kDa subunit of signal recognition particle is sufficient for the interaction with signal sequences. Lütcke, H., High, S., Römisch, K., Ashford, A.J., Dobberstein, B. EMBO J. (1992) [Pubmed]
  7. Assembly of the human signal recognition particle (SRP): overlap of regions required for binding of protein SRP54 and assembly control. Yin, J., Yang, C.H., Zwieb, C. RNA (2001) [Pubmed]
  8. Protein SRP54 of human signal recognition particle: cloning, expression, and comparative analysis of functional sites. Gowda, K., Black, S.D., Moeller, I., Sakakibara, Y., Liu, M.C., Zwieb, C. Gene (1998) [Pubmed]
  9. S-domain assembly of the signal recognition particle. Sauer-Eriksson, A.E., Hainzl, T. Curr. Opin. Struct. Biol. (2003) [Pubmed]
  10. RNA interference of signal peptide-binding protein SRP54 elicits deleterious effects and protein sorting defects in trypanosomes. Liu, L., Liang, X.H., Uliel, S., Unger, R., Ullu, E., Michaeli, S. J. Biol. Chem. (2002) [Pubmed]
  11. Crystal structure of the conserved subdomain of human protein SRP54M at 2.1 A resolution: evidence for the mechanism of signal peptide binding. Clemons, W.M., Gowda, K., Black, S.D., Zwieb, C., Ramakrishnan, V. J. Mol. Biol. (1999) [Pubmed]
  12. A chloroplast homologue of the signal recognition particle subunit SRP54 is involved in the posttranslational integration of a protein into thylakoid membranes. Li, X., Henry, R., Yuan, J., Cline, K., Hoffman, N.E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  13. A structure for the signal sequence binding protein SRP54: 3D reconstruction from STEM images of single molecules. Czarnota, G.J., Andrews, D.W., Farrow, N.A., Ottensmeyer, F.P. J. Struct. Biol. (1994) [Pubmed]
  14. Binding site of the M-domain of human protein SRP54 determined by systematic site-directed mutagenesis of signal recognition particle RNA. Gowda, K., Chittenden, K., Zwieb, C. Nucleic Acids Res. (1997) [Pubmed]
  15. Genetic and biochemical analysis of the fission yeast ribonucleoprotein particle containing a homolog of Srp54p. Selinger, D., Brennwald, P., Althoff, S., Reich, C., Hann, B., Walter, P., Wise, J.A. Nucleic Acids Res. (1994) [Pubmed]
  16. Induced structural changes of 7SL RNA during the assembly of human signal recognition particle. Kuglstatter, A., Oubridge, C., Nagai, K. Nat. Struct. Biol. (2002) [Pubmed]
  17. A GTPase cycle in initiation of protein translocation across the endoplasmic reticulum membrane. Miller, J.D., Walter, P. Ciba Found. Symp. (1993) [Pubmed]
  18. Molecular evolution of SRP cycle components: functional implications. Althoff, S., Selinger, D., Wise, J.A. Nucleic Acids Res. (1994) [Pubmed]
  19. Signal recognition particle components in the nucleolus. Politz, J.C., Yarovoi, S., Kilroy, S.M., Gowda, K., Zwieb, C., Pederson, T. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  20. Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B(1) can disrupt protein targeting. Singh, J., Dani, H.M., Sharma, R., Steinberg, P. Cell Biochem. Funct. (2006) [Pubmed]
  21. Expression, purification, and crystallography of the conserved methionine-rich domain of human signal recognition particle 54 kDa protein. Gowda, K., Clemons, W.M., Zwieb, C., Black, S.D. Protein Sci. (1999) [Pubmed]
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