Dynamic architecture of the peroxisomal import receptor Pex5p

Abstract

The majority of peroxisomal matrix proteins are recognized by the import receptor Pex5p. The receptor is dynamic in terms of its overall architecture and association with the peroxisomal membrane. It participates in different protein complexes during the translocation of cargos from the cytosol to the peroxisomal matrix. Its sequence comprises two structurally and functionally autonomous parts. The N-terminal segment interacts with several peroxins that assemble into distinct protein complexes during cargo translocation. Despite evidence for alpha-helical binding motifs for some of these components (Pex13p, Pex14p) its overall appearance is that of a molten globule and folding/unfolding transitions may play a critical role in its function. In contrast, most of the C-terminal part of the receptor folds into a ring-like alpha-helical structure and binds folded and functionally intact peroxisomal targets that bear a C-terminal peroxisomal targeting signal type-1. Some of these targets also bind to secondary binding sites of the receptor.