Practice question

Peroxisomal biogenesis uses two soluble receptors distinguishing two signals. Pex5 70 kDa primary receptor PTS1 pathway handling bulk matrix proteins catalase ACOX1 DBP. Structurally N-terminal half intrinsically disordered contains multiple WXXXF motifs interacting peroxisomal membrane docking protein Pex14 N-terminal domain plus cysteine ubiquitination sites recycling amphipathic helices; C-terminal seven tetratricopeptide repeats TPR 34 aa folding two half-rings superhelical clamp central cavity accommodating C-terminal tripeptide Ser-Lys-Leu water-mediated hydrogen bonds explaining tolerance variant residues. Mechanism stepwise: cytosolic Pex5 binds cargo high affinity escorted peroxisome where N-domain inserts interacting Pex14 Pex13 cargo released matrix through transient pore oligomerized Pex5 Pex14 channel large folded protein passage. Pex5 itself enters lumen transiently then recycled. Pex7 WD40 propeller recognizes PTS2 N-terminal nonapeptide RLX5HL thiolase phytanoyl CoA hydroxylase alkyl DHAP synthase; Pex19 cytosolic chaperone peroxisomal membrane proteins, Rab5 small GTPase marks early endosome fusion unrelated. Defective Pex5 mutations cause Zellweger cytosolic catalase puncta loss very long chain fatty acid accumulation clinically devastating lethal infantile presentation.