Practice question

While most secretory and membrane proteins in mammals rely on SRP-dependent co-translational targeting, small proteins less than about one hundred residues and many soluble yeast proteins synthesized completely before targeting rely on post-translational translocation requiring distinct chaperone system. Cytosolic Hsp70 homologs Ssa1 maintain substrate unfolded, then Sec62/Sec63 heterodimer together with Sec71/Sec72 accessory proteins in yeast forms heptameric Sec complex around Sec61 channel to recruit substrate. Lumenal Hsp70 BiP, called Kar2 in Saccharomyces, binds DnaJ domain of Sec63 which stimulates its ATPase activity. ATP-bound BiP recruited to incoming chain hydrolyzes ATP to ADP, converting to closed high-affinity conformation clamping onto hydrophobic patches, preventing back-sliding through channel. Nucleotide exchange factors Sil1 and Grp170 promote ADP release for BiP recycling, allowing repeated capture events that rectify Brownian motion into directional pulling force. Each ATP hydrolysis cycle advances chain inward independent of ribosome. SRP, Sec61 alone without BiP and Ran-GTP dependent nuclear import do not provide ATP-driven pulling for this mode, so BiP is essential ATPase converting chemical energy into vectorial movement for post-translational ER entry and secretory pathway maintenance.