Abstract
Co-translational protein targeting to membranes is a universally conserved process. Central steps include cargo recognition by the signal recognition particle and handover to the Sec translocon. Here we present snapshots of key co-translational-targeting complexes solved by cryo-electron microscopy at near-atomic resolution, establishing the molecular contacts between the Escherichia coli translating ribosome, the signal recognition particle and the translocon. Our results reveal the conformational changes that regulate the latching of the signal sequence, the release of the heterodimeric domains of the signal recognition particle and its receptor, and the handover of the signal sequence to the translocon. We also observe that the signal recognition particle and the translocon insert-specific structural elements into the ribosomal tunnel to remodel it, possibly to sense nascent chains. Our work provides structural evidence for a conformational state of the signal recognition particle and its receptor primed for translocon binding to the ribosome–nascent chain complex.
Highlights
Co-translational protein targeting to membranes is a universally conserved process
We identified a conformation of the signal recognition particle (SRP)–SRP receptor (SR)-targeting complex in which the SR G domain is bound to the SRP RNA tetraloop, whereas the N domain of Ffh is still attached to the RNC at uL23 and uL29 (Fig. 1; Fig. 3a–b)
Our RNC–SR- and RNC–SRP–SR-targeting complexes imply an interplay between the signal sequence (SS), the fingerloop of the M domain and the GM linker: binding of the SRP to the ribosome involves the formation of interactions between the SRP NG domain, uL23 and uL29, and positioning of the M domain together with the SRP RNA next to the tunnel exit (Fig. 6a)
Summary
Co-translational protein targeting to membranes is a universally conserved process. Central steps include cargo recognition by the signal recognition particle and handover to the Sec translocon. This process involves the recruitment of intricate cellular machineries that are conserved throughout all forms of life This includes a ribonucleoprotein complex termed the signal recognition particle (SRP), the SRP receptor (SR) and the translocation machinery or Sec translocon[3,4,5,6]. Conformational rearrangements in the SRP–SR heterodimer[15,16,19] lead to detachment of the SRP–SR NG dimer from the RNC8,20,21 to form the ‘closed’ state[22] At this stage, the Sec translocon binds to the RNC–SRP–SR complex, and the heterodimerized NG domains of SRP and SR dock at the distal end of the SRP RNA hairpin[23,24,25], forming an ‘activated’ state where GTP hydrolysis is triggered[26]. Our results provide evidence for an active role played by the SRP and the Sec translocon on the RNC during cargo recognition and handover
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