Assembly and Function of the Signal Recognition Particle from Archaea

  • Elisabeth Sauer-Eriksson
  • Shenghua Huang
  • Tobias Hainzl
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)


The signal recognition particle (SRP) is a protein-RNA complex that associates with ribosomes to mediate co-translational targeting of membrane and secretory proteins to biological membranes. The universally conserved core of SRP consists of SRP RNA and the SRP54 protein, and plays the key role in signal-sequence recognition and binding to the SRP receptor. Critical for SRP function is communication between the two conserved SRP54 domains, the GTPase- and the M-domain, so that signal-sequence binding at the M domain directs receptor binding at the GTPase domain. The structural basis for signal-sequence binding by SRP and subsequent signaling is still poorly understood. By studying the structures of the SRP RNA in its free form as well as in complex with its different protein partners, we have made steady progress towards the elucidation of structural states of the SRP, using the archaeon Methanococcus jannaschii as model system. Together with other structures of SRP proteins and RNA-protein complexes, these structures provide new insights into the mechanisms of SRP-mediated protein targeting.


Protein transport Signal recognition particle X-ray structure Methanococcus jannaschii Signal sequence 


  1. 1.
    Andersen ES, Rosenblad MA, Larsen N, Westergaard JC, Burks J, Wower IK, Wower J, Gorodkin J, Samuelsson T, Zwieb C (2006) The tmRDB and SRPDB resources. Nucleic Acids Res 34((Database issue)):D163–D168CrossRefGoogle Scholar
  2. 2.
    Batey RT, Rambo RP, Lucast L, Rha B, Doudna JA (2000) Crystal structure of the ribonucleoprotein core of the signal recognition particle. Science 287(5456):1232–1239CrossRefADSGoogle Scholar
  3. 3.
    Bradshaw N, Neher SB, Booth DS, Walter P (2009) Signal sequences activate the catalytic switch of SRP RNA. Science 323(5910):127–130CrossRefADSGoogle Scholar
  4. 4.
    Bradshaw N, Walter P (2007) The signal recognition particle (SRP) RNA links conformational changes in the SRP to protein targeting. Mol Biol Cell 18(7):2728–2734CrossRefGoogle Scholar
  5. 5.
    Chu F, Shan SO, Moustakas DT, Alber F, Egea PF, Stroud RM, Walter P, Burlingame AL (2004) Unraveling the interface of signal recognition particle and its receptor by using chemical cross-linking and tandem mass spectrometry. Proc Natl Acad Sci USA 101(47):16454–16459CrossRefADSGoogle Scholar
  6. 6.
    Doudna JA, Batey RT (2004) Structural insights into the signal recognition particle. Annu Rev Biochem 73:539–557CrossRefGoogle Scholar
  7. 7.
    Egea PF, Shan SO, Napetschnig J, Savage DF, Walter P, Stroud RM (2004) Substrate twinning activates the signal recognition particle and its receptor. Nature 427(6971):215–221CrossRefADSGoogle Scholar
  8. 8.
    Egea PF, Stroud RM, Walter P (2005) Targeting proteins to membranes: structure of the signal recognition particle. Curr Opin Struct Biol 15(2):213–220CrossRefGoogle Scholar
  9. 9.
    Focia PJ, Shepotinovskaya IV, Seidler JA, Freymann DM (2004) Heterodimeric GTPase core of the SRP targeting complex. Science 303(5656):373–377CrossRefADSGoogle Scholar
  10. 10.
    Freymann DM, Keenan RJ, Stroud RM, Walter P (1997) Structure of the conserved GTPase domain of the signal recognition particle. Nature 385(6614):361–364CrossRefADSGoogle Scholar
  11. 11.
    Grudnik P, Bange G, Sinning I (2009) Protein targeting by the signal recognition particle. Biol Chem 390(8):775–782CrossRefGoogle Scholar
  12. 12.
    Hainzl T, Huang S, Sauer-Eriksson AE (2002) Structure of the SRP19 RNA complex and implications for signal recognition particle assembly. Nature 417(6890):767–771CrossRefADSGoogle Scholar
  13. 13.
    Hainzl T, Huang S, Sauer-Eriksson AE (2005) Structural insights into SRP RNA: an induced fit mechanism for SRP assembly. RNA 11(7):1043–1050CrossRefGoogle Scholar
  14. 14.
    Hainzl T, Huang S, Sauer-Eriksson AE (2007) Interaction of signal-recognition particle 54 GTPase domain and signal-recognition particle RNA in the free signal-recognition particle. Proc Natl Acad Sci USA 104(38):14911–14916CrossRefADSGoogle Scholar
  15. 15.
    Hainzl T, Huang S, Merilainen G, Brannstrom K, Sauer-Eriksson AE (2011) Structural basis of signal-sequence recognition by the signal recognition particle. Nat Struct Mol Biol 18(3):389–391Google Scholar
  16. 16.
    Halic M, Becker T, Pool MR, Spahn CM, Grassucci RA, Frank J, Beckmann R (2004) Structure of the signal recognition particle interacting with the elongation-arrested ribosome. Nature 427(6977):808–814CrossRefADSGoogle Scholar
  17. 17.
    Halic M, Blau M, Becker T, Mielke T, Pool MR, Wild K, Sinning I, Beckmann R (2006) Following the signal sequence from ribosomal tunnel exit to signal recognition particle. Nature 444(7118):507–511CrossRefADSGoogle Scholar
  18. 18.
    Halic M, Gartmann M, Schlenker O, Mielke T, Pool MR, Sinning I, Beckmann R (2006) Signal recognition particle receptor exposes the ribosomal translocon binding site. Science 312(5774):745–747CrossRefADSGoogle Scholar
  19. 19.
    Jagath JR, Matassova NB, de Leeuw E, Warnecke JM, Lentzen G, Rodnina MV, Luirink J, Wintermeyer W (2001) Important role of the tetraloop region of 4.5S RNA in SRP binding to its receptor FtsY. RNA 7(2):293–301CrossRefGoogle Scholar
  20. 20.
    Janda CY, Li J, Oubridge C, Hernandez H, Robinson CV, Nagai K (2010) Recognition of a signal peptide by the signal recognition particle. Nature 465(7297):507–510CrossRefADSGoogle Scholar
  21. 21.
    Keenan RJ, Freymann DM, Walter P, Stroud RM (1998) Crystal structure of the signal sequence binding subunit of the signal recognition particle. Cell 94(2):181–191CrossRefGoogle Scholar
  22. 22.
    Lee HC, Bernstein HD (2001) The targeting pathway of Escherichia coli presecretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal. Proc Natl Acad Sci USA 98(6):3471–3476CrossRefADSGoogle Scholar
  23. 23.
    Montoya G, Svensson C, Luirink J, Sinning I (1997) Crystal structure of the NG domain from the signal-recognition particle receptor FtsY. Nature 385(6614):365–368CrossRefADSGoogle Scholar
  24. 24.
    Nagai K, Oubridge C, Kuglstatter A, Menichelli E, Isel C, Jovine L (2003) Structure, function and evolution of the signal recognition particle. EMBO J 22(14):3479–3485CrossRefGoogle Scholar
  25. 25.
    Oubridge C, Kuglstatter A, Jovine L, Nagai K (2002) Crystal structure of SRP19 in complex with the S domain of SRP RNA and its implication for the assembly of the signal recognition particle. Mol Cell 9(6):1251–1261CrossRefGoogle Scholar
  26. 26.
    Peluso P, Shan SO, Nock S, Herschlag D, Walter P (2001) Role of SRP RNA in the GTPase cycles of Ffh and FtsY. Biochemistry 40(50):15224–15233CrossRefGoogle Scholar
  27. 27.
    Poritz MA, Bernstein HD, Strub K, Zopf D, Wilhelm H, Walter P (1990) An E. coli ribonucleoprotein containing 4.5S RNA resembles mammalian signal recognition particle. Science 250(4984):1111–1117CrossRefADSGoogle Scholar
  28. 28.
    Ribes V, Romisch K, Giner A, Dobberstein B, Tollervey D (1990) E. coli 4.5S RNA is part of a ribonucleoprotein particle that has properties related to signal recognition particle. Cell 63(3):591–600CrossRefGoogle Scholar
  29. 29.
    Rosendal KR, Wild K, Montoya G, Sinning I (2003) Crystal structure of the complete core of archaeal signal recognition particle and implications for interdomain communication. Proc Natl Acad Sci USA 100(25):14701–14706CrossRefADSGoogle Scholar
  30. 30.
    Sauer-Eriksson AE, Hainzl T (2003) S-domain assembly of the signal recognition particle. Curr Opin Struct Biol 13(1):64–70CrossRefGoogle Scholar
  31. 31.
    Schaffitzel C, Oswald M, Berger I, Ishikawa T, Abrahams JP, Koerten HK, Koning RI, Ban N (2006) Structure of the E. coli signal recognition particle bound to a translating ribosome. Nature 444(7118):503–506CrossRefADSGoogle Scholar
  32. 32.
    Spanggord RJ, Siu F, Ke A, Doudna JA (2005) RNA-mediated interaction between the peptide-binding and GTPase domains of the signal recognition particle. Nat Struct Mol Biol 12(12):1116–1122CrossRefGoogle Scholar
  33. 33.
    von Heijne G (1985) Signal sequences. The limits of variation. J Mol Biol 184(1):99–105CrossRefGoogle Scholar
  34. 34.
    Zhang X, Rashid R, Wang K, Shan SO (2010) Sequential checkpoints govern substrate selection during cotranslational protein targeting. Science 328(5979):757–760CrossRefADSGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Elisabeth Sauer-Eriksson
    • 1
  • Shenghua Huang
    • 1
  • Tobias Hainzl
    • 1
  1. 1.Department of ChemistryUmeå UniversityUmeåSweden

Personalised recommendations