Chapter 13: Protein Targeting to Membranes & Organelles

Protein Targeting to Membranes & Organelles begins by defining the secretory pathway, explaining how the signal recognition particle (SRP) and N-terminal signal sequences target ribosomes to the ER membrane for cotranslational translocation via the Sec61 translocon. The text outlines the topology of integral membrane proteins, distinguishing between Type I, II, III, and IV proteins based on their internal stop-transfer anchor and signal-anchor sequences, as well as the unique insertion of tail-anchored and GPI-anchored proteins. Significant attention is given to protein modifications within the rough ER, such as N-linked glycosylation via dolichol phosphate, disulfide bond formation catalyzed by protein disulfide isomerase (PDI), and folding assistance provided by chaperones like BiP, calnexin, and calreticulin. The summary further explores quality control mechanisms, including the unfolded-protein response (UPR) and ER-associated degradation (ERAD), which dislocates misfolded proteins to the cytosol for ubiquitin-mediated proteasomal destruction. The discussion then shifts to organelle-specific transport, describing how amphipathic matrix-targeting sequences guide proteins into mitochondria through Tom and Tim complexes, a process driven by ATP hydrolysis and the proton-motive force. Parallel mechanisms in chloroplasts are reviewed, involving Toc and Tic complexes for stromal import and specialized pathways for thylakoid targeting. The chapter also covers the import of folded proteins into peroxisomes via PTS1 signals and Pex receptors. Finally, it elucidates nuclear transport, detailing the structure of the nuclear pore complex (NPC) and the function of nuclear-localization signals (NLS) and nuclear-export signals (NES). This section explains how the Ran GTPase gradient powers the unidirectional movement of importins and exportins, and describes the distinct, Ran-independent mechanism used for mRNP export via NXF1 and NXT1.