Figure 5. Proposed cargo handover mechanism of co-translational protein targeting.

Schematic of the early, closed and activated/quaternary targeting complexes ending with the RNC in complex with the Sec translocon. Initially the SR binds to the SRP RNC complex at the tetraloop side of the SRP RNA, followed by repositioning and docking of the NG heterodimer to the distal region of SRP RNA. GTPase activation becomes possible upon conformational change in the SRP RNA that accommodates NG heterodimer between the SRP RNA and the ribosomal surface. Signal sequence handover is favored for longer nascent chains that can reach Sec translocon. Sec translocon will then displace the M-domain and SRP on the ribosome exit tunnel to complete the targeting cycle.