1. Institute of Biochemistry, Charité, University Medical School, Humboldt University of Berlin, Monbijoustrasse 2, 10117 Berlin, Germany
2. University of Manchester, School of Biological Sciences, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
3. Institute of Medical Physics and Biophysics, Charité, University Medical School, Humboldt University of Berlin, Ziegelstrasse 9, 10117 Berlin, Germany
4. Howard Hughes Medical Institute, Health Research Incorporated, Wadsworth Center, Empire State Plaza, Albany, New York 12201, and Department of Biomedical Sciences, State University of New York at Albany, Albany, New York 12222, USA

Correspondence to: Roland Beckmann¹ Email: roland.beckmann@charite.de
Coordinates of the atomic model of SRP have been deposited in the PDB under accession number 1RY1. The cryo-EM map has been deposited in the 3D-EM database (EMBL–European Bioinformatics Institute, Cambridge, UK) under accession number EMD-1063.

Abstract

Cotranslational translocation of proteins across or into membranes is a vital process in all kingdoms of life. It requires that the translating ribosome be targeted to the membrane by the signal recognition particle (SRP), an evolutionarily conserved ribonucleoprotein particle. SRP recognizes signal sequences of nascent protein chains emerging from the ribosome. Subsequent binding of SRP leads to a pause in peptide elongation and to the ribosome docking to the membrane-bound SRP receptor. Here we present the structure of a targeting complex consisting of mammalian SRP bound to an active 80S ribosome carrying a signal sequence. This structure, solved to 12 Å by cryo-electron microscopy, enables us to generate a molecular model of SRP in its functional conformation. The model shows how the S domain of SRP contacts the large ribosomal subunit at the nascent chain exit site to bind the signal sequence, and that the Alu domain reaches into the elongation-factor-binding site of the ribosome, explaining its elongation arrest activity.

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