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GTP binding and hydrolysis by the signal recognition particle during initiation of protein translocation

Nature volume 366, pages 351–354 (1993)Cite this article

Abstract

THE signal recognition particle (SRP) consists of one RNA and six protein subunits1,2. The N-terminal domain of the 54K subunit contains a putative GTP-binding site, whereas the C-terminal domain binds signal sequences and SRP RNA3–7. Binding of SRP to the signal sequence as it emerges from the ribosome creates a cytosolic targeting complex containing the nascent polypeptide chain, the translating ribosome, and SRP8. This complex is directed to the endoplasmic reticulum membrane as a result of its interaction with the SRP receptor9–11, a membrane protein composed of two subunits, SRα and SRβ, each of which also contains a GTP-binding domain12,13. In the presence of GTP, SRP receptor binding to SRP causes the latter to dissociate from both the signal sequence and the ribosome13,14. GTP is then hydrolysed so that SRP can be released from the SRP receptor and returned to the cytosol15. Here we show that the 54K subunit (Mr 54,000) of SRP (SRP54) is a GTP-binding protein stabilized in a nucleotide-free state by signal sequences, and that the SRP receptor both increases the affinity of SRP54 for GTP and activates its GTPase. We propose that nucleotide-mediated conformational changes in SRP54 regulate the release of signal sequences and the docking of ribosomes at the endoplasmic reticulum.

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Author notes

  1. Lila Gierasch: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9041, USA

  2. Reid Gilmore: Department of Biochemistry, University of Massachusetts, Worchester, Massachusetts 01655-0001, USA

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of California Medical School, San Francisco, California, 94143-0448, USA

    Joshua D. Miller, Heike Wilhelm, Lila Gierasch, Reid Gilmore & Peter Walter

Authors
  1. Joshua D. Miller
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  2. Heike Wilhelm
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  4. Reid Gilmore
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Miller, J., Wilhelm, H., Gierasch, L. et al. GTP binding and hydrolysis by the signal recognition particle during initiation of protein translocation. Nature 366, 351–354 (1993). https://doi.org/10.1038/366351a0

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