title: Following the signal sequence from ribosomal tunnel exit to signal recognition particle.
abstract: Membrane and secretory proteins can be co-translationally inserted into or translocated across the membrane. This process is dependent on signal sequence recognition on the ribosome by the signal recognition particle (SRP), which results in targeting of the ribosome-nascent-chain complex to the protein-conducting channel at the membrane. Here we present an ensemble of structures at subnanometre resolution, revealing the signal sequence both at the ribosomal tunnel exit and in the bacterial and eukaryotic ribosome-SRP complexes. Molecular details of signal sequence interaction in both prokaryotic and eukaryotic complexes were obtained by fitting high-resolution molecular models. The signal sequence is presented at the ribosomal tunnel exit in an exposed position ready for accommodation in the hydrophobic groove of the rearranged SRP54 M domain. Upon ribosome binding, the SRP54 NG domain also undergoes a conformational rearrangement, priming it for the subsequent docking reaction with the NG domain of the SRP receptor. These findings provide the structural basis for improving our understanding of the early steps of co-translational protein sorting.
authors.affiliation: Gene Center, Department of Chemistry and Biochemistry, University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Halic
authors.forename: Michael
authors.initials: M
authors.lastname: Blau
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mielke
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pool
authors.forename: Klemens
authors.initials: K
authors.lastname: Wild
authors.forename: Irmgard
authors.initials: I
authors.lastname: Sinning
authors.forename: Roland
authors.initials: R
authors.lastname: Beckmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D004926:Escherichia coli / Q000235:genetics; D008322:Mammals / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals; D012335:RNA, Ribosomal / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry*; D018271:Signal Recognition Particle / Q000737:chemistry*
chemical_list: D021382:Protein Sorting Signals; D012335:RNA, Ribosomal; D018271:Signal Recognition Particle