Practice question

N-terminal signal peptides exhibit tripartite organization essential for targeting and cleavage: positively charged n-region with one to three basic residues, hydrophobic core h-region of seven to twelve aliphatic residues forming alpha-helix, and polar c-region containing signal peptidase recognition motif Ala-X-Ala at positions minus three and minus one relative to cleavage site, often followed by small residues. Once nascent chain enters ER lumen through Sec61 channel, signal peptidase complex anchored on lumenal face performs co-translational cleavage. Heteromeric complex includes two catalytic subunits SEC11A and SEC11C that are serine proteases of S26 family using Ser-His-Asp catalytic triad, plus accessory subunits SPCS1, SPCS2, SPCS3 stabilizing assembly and positioning active site near membrane interface. Catalytic serine attacks carbonyl after c-region, hydrolyzing bond and liberating mature protein from membrane-tethered signal. Cleaved signal peptides further degraded by intramembrane signal peptide peptidase. Sec61 itself lacks proteolytic activity, SRP receptor only delivers, translocon pore conducts, so efficient cleavage is prerequisite for subsequent folding, N-glycosylation and trafficking beyond ER, preventing retention as membrane-anchored precursor that could disrupt membrane integrity.