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SRP RNA Remodeling by SRP68 Explains Its Role in Protein Translocation

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Science  04 Apr 2014:
Vol. 344, Issue 6179, pp. 101-104
DOI: 10.1126/science.1249094

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Dissecting SRP

In the secretory pathway, inserting transmembrane and secretory proteins into and through hydrophobic cell membranes is facilitated by a highly conserved RNA and protein-containing molecular machine, the signal recognition particle (SRP). Grotwinkel et al. (p. 101) determined the x-ray crystal structures of human SRP RNA (7SL RNA) bound to the RNA-binding domain (RBD) of the protein SRP subunit SRP68, both in the presence and absence of the SRP19 subunit. The 7SL RNA is remodeled by the SRP68-RBD, which bends one domain of the RNA and remodels a loop, exposing two nucleotides, which allow direct interaction with the ribosome. The findings explain how the SRP RNA drives translation elongation arrest, which is required for membrane insertion.

Abstract

The signal recognition particle (SRP) is central to membrane protein targeting; SRP RNA is essential for SRP assembly, elongation arrest, and activation of SRP guanosine triphosphatases. In eukaryotes, SRP function relies on the SRP68-SRP72 heterodimer. We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19. SRP68-RBD is a tetratricopeptide-like module that binds to a RNA three-way junction, bends the RNA, and inserts an α-helical arginine-rich motif (ARM) into the major groove. The ARM opens the conserved 5f RNA loop, which in ribosome-bound SRP establishes a contact to ribosomal RNA. Our data provide the structural basis for eukaryote-specific, SRP68-driven RNA remodeling required for protein translocation.

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