Fig. 7: Model of TM domain capture upon exit from the ribosomal tunnel.
From: Ribosome-bound Get4/5 facilitates the capture of tail-anchored proteins by Sgt2 in yeast
(I) A sequence with the characteristics of a hydrophobic α-helical transmembrane domain emerges from the peptidyl transferase center and enters the ribosomal tunnel. At that point, SRP and Get4/5 cycle on and off ribosomes, as it remains unclear if the hydrophobic sequence is a TM domain (internal transmembrane domain) or a TA sequence (C-terminal transmembrane domain). (II) In case translation continues, the hydrophobic sequence remains ribosome-bound as part of the nascent chain and becomes an internal TM domain. (III) Upon exit from the tunnel, the internal TM domain is recognized by SRP. As SRP now binds with high affinity, the binding and release cycle of Get4/5, and concurrently Sgt2, is interrupted. (IV) If translation termination occurs immediately after synthesis of the hydrophobic domain, which is then termed TA sequence, SRP is not efficiently recruited to the now non-translating ribosome or the released TA sequence. (V) In this case, Get4/5, and via Get4/5 also Sgt2, continue to sample ribosomes and Sgt2 can capture the TA sequence directly upon arrival at the tunnel exit. Ribosome (light gray), nascent chain (dark gray) TA sequence (red), TM domain (yellow), Get4 (brown) Get5 (light blue), Sgt2 (dark blue), SRP (green). TA (C-terminal tail-anchor sequence) and TM (internal transmembrane domain).
