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Structure of the most conserved internal loop in SRP RNA

Nature Structural Biology volume 6, pages 634–638 (1999)Cite this article

Abstract

The signal recognition particle (SRP) directs translating ribosomes to the protein translocation apparatus of endoplasmic reticulum (ER) membrane or the bacterial plasma membrane. The SRP is universally conserved, and in prokaryotes consists of two essential subunits, SRP RNA and SRP54, the latter of which binds to signal sequences on the nascent protein chains. Here we describe the solution NMR structure of a 28-mer RNA composing the most conserved part of SRP RNA to which SRP54 binds. Central to this function is a six-nucleotide internal loop that assumes a novel Mg2+-dependent structure with unusual cross-strand interactions; besides a cross-strand A/A stack, two guanines form hydrogen bonds with opposite-strand phosphates. The structure completely explains the phylogenetic conservation of the loop bases, underlining its importance for SRP54 binding and SRP function.

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Figure 1: a, Secondary structure of E. coli 4.5S RNA and its interaction site with Ffh (shown in gray as two-domain model).
Figure 2: NMR spectra of exchangeable protons of the SRP 28-mer.
Figure 3: Portion of the 2D NOE spectrum in D2O (mixing time = 200 ms) in the presence of Mg2+ showing aromatic to anomeric NOEs.
Figure 4: The NMR structure of the SRP 28-mer.

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Acknowledgements

This research was supported by an NIH grant to T.L.J. and an NSF grant to U.S. The NMR instrument was purchased with funds from an NIH grant. P.W. is an investigator of the Howard Hughes Medical Institute. We acknowledge the UCSF Computer Graphics laboratory, also supported by an NIH grant.

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Author notes

  1. Peter Lukavsky

    Present address: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, 94305-5400

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, University of California San Francisco, 513 Parnassus, San Francisco, 94143-0446, CA

    Uli Schmitz, Thomas L. James & Peter Lukavsky

  2. Department of Biochemistry and Biophysics, 513 Parnassus, San Francisco, 94143-0446, CA

    Peter Walter

  3. Howard Hughes Medical Institute, University of California San Francisco, 513 Parnassus, San Francisco, 94143-0446, CA

    Peter Walter

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  1. Uli Schmitz
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Correspondence to Uli Schmitz.

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Schmitz, U., James, T., Lukavsky, P. et al. Structure of the most conserved internal loop in SRP RNA. Nat Struct Mol Biol 6, 634–638 (1999). https://doi.org/10.1038/10683

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