Cryo-EM structure of the ribosome–SecYE complex in the membrane environment

• Published in: Nature structural & molecular biology Vol. 18; no. 5; pp. 614 - 621
• Main Authors: Frauenfeld, Jens, Gumbart, James, Sluis, Eli O van der, Funes, Soledad, Gartmann, Marco, Beatrix, Birgitta, Mielke, Thorsten, Berninghausen, Otto, Becker, Thomas, Schulten, Klaus, Beckmann, Roland
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2011; Nature Publishing Group
• Subjects: 631/337/574/1789; 631/45/612/1237; 631/535/1258/1259; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Cell Membrane - metabolism; Cryoelectron Microscopy; Crystal structure; Escherichia coli; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Life Sciences; Lipids; Lipoproteins, HDL - chemistry; Lipoproteins, HDL - metabolism; Medicin och hälsovetenskap; Membrane Biology; Membrane proteins; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Models, Molecular; Molecular biology; Physiological aspects; Polypeptides; Protein Structure; Protein Transport; Proteins; Ribonucleic acid; Ribosomes; Ribosomes - chemistry; RNA; SEC Translocation Channels; Signal Recognition Particle - physiology; Structure; United States; Germany
• ISSN: 1545-9993; 1545-9985; 1545-9985
• DOI: 10.1038/nsmb.2026

A cryo-EM structure of the bacterial ribosome–SecYEG complex in a so-called Nanodisc allows for the molecular interpretation of the SecYEG complex in its natural lipid bilayer environment. Molecular dynamics simulations based on the structure reveal stable interactions between ribosomal RNA and the membrane that may contribute to the insertase activity of the protein-conducting channel. The ubiquitous SecY–Sec61 complex translocates nascent secretory proteins across cellular membranes and integrates membrane proteins into lipid bilayers. Several structures of mostly detergent-solubilized Sec complexes have been reported. Here we present a single-particle cryo-EM structure of the SecYEG complex in a membrane environment, bound to a translating ribosome, at subnanometer resolution. Using the SecYEG complex reconstituted in a so-called Nanodisc, we could trace the nascent polypeptide chain from the peptidyltransferase center into the membrane. The reconstruction allowed for the identification of ribosome–lipid interactions. The rRNA helix 59 (H59) directly contacts the lipid surface and appears to modulate the membrane in immediate vicinity to the proposed lateral gate of the protein-conducting channel (PCC). On the basis of our map and molecular dynamics simulations, we present a model of a signal anchor–gated PCC in the membrane.