Practice question

Specificity of signal recognition particle for hydrophobic targeting signals resides within C-terminal M domain of 54 kilodalton subunit SRP54. Structural analyses of bacterial homolog Ffh and mammalian SRP54 show M domain folds into deep groove lined almost exclusively with methionine side chains whose flexible thioether and long aliphatic chain create plastic hydrophobic bristle adaptable to varied signal sequence compositions and lengths. Basic residues surrounding groove interact with phosphate backbone of 7SL RNA and ribosomal proteins L23 and L29 near peptide exit tunnel. Adjacent NG GTPase domains dimerize with SRP receptor SRα via GTP-dependent interaction but do not contact signal directly. Upon signal accommodating as alpha-helix inside groove, conformational change extends to linker connecting M and NG domains, signaling Alu domain to pause translation. ATPase or BiP domains absent from SRP. This methionine-rich architecture explains how single particle binds hundreds of diverse ER targeting signals with high affinity yet promiscuous selectivity, ensuring efficient capture of secretory proteins early during synthesis preventing cytosolic mislocalization, aggregation and degradation by proteasome quality control and maintaining secretory flux.