Which of the following recognizes the signal sequence of nascent proteins targeting the ER?
Early sorting of nascent secretory and membrane proteins is performed by signal recognition particle, conserved ribonucleoprotein containing 7SL RNA scaffold and six protein subunits. When hydrophobic signal sequence of about eight to twelve non-polar residues emerges from ribosomal exit tunnel, methionine-rich M domain of SRP54 forms flexible hydrophobic groove whose abundance of sulfur-containing methionine side chains allows plastic accommodation of diverse signal sequences via induced fit. Binding is communicated through 7SL RNA to Alu domain comprised of SRP9 and SRP14 heterodimer that docks at elongation factor binding site, temporarily pausing translation to prevent premature folding and aggregation in cytosol. SRP-ribosome-nascent chain complex then diffuses to ER where GTP-dependent interaction with heterodimeric SRP receptor made of SRα and SRβ GTPases delivers complex to Sec61 channel for hand-off. Ran-GTP controls nuclear import via importins, KDEL receptor retrieves escaped ER chaperones via COPI, Rab GTPases govern vesicle tethering and fusion specificity, none directly scan ribosome exit tunnel for hydrophobic nascent signals at this early checkpoint of protein sorting to ER lumen.
Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 13: SRP Recognizes Signal Sequences.