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.

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

“…Conversely, Harper et al (2003) saw no effect of HSP70 on the binding of a PTS1 peptide to Pex5p. However, there have been several reports which support the conformational change of Pex5p when bound to a cargo molecule (Madrid et al, 2004;Costa-Rodrigues et al, 2005;Stanley et al, 2006;Moscicka et al, 2007). An N526K mutation at the C-terminus of HsPEX5L (equivalent to N489K in PEX5S; Table 1 and Figure 2B) has been shown to block the binding of PTS1 and induce a conformational shift in the N-terminus.…”

Trafficking and Gating of Hyperpolarization-activated Cyclic Nucleotide-gated Channels Are Regulated by Interaction with Tetratricopeptide Repeat-containing Rab8b-interacting Protein (TRIP8b) and Cyclic AMP at Distinct Sites

“…Recent studies have demonstrated that in the brain, native HCN channels co-purify with TRIP8b (also called peroxin 5-like protein, PEX5L) (9), and consistent with a role as an auxiliary HCN channel subunit, TRIP8b regulates HCN channel trafficking, voltage gating, and kinetics in vitro and in vivo (9 -11). The TRIP8b C terminus is highly homologous to the peroxisomal import protein, peroxin 5 (PEX5), and is comprised of two sets of three tetratricopeptide repeat (TPR) domains separated by a linker, a C-terminal tail, and a region enriched in acidic amino acids N-terminal to the first TPR set that is conserved in both PEX5 and TRIP8b (10,12). The N terminus of TRIP8b shares no sequence homology to PEX5 and is subject to extensive alternative splicing that leads to expression of multiple distinct TRIP8b isoforms.…”

Identification of Ubiquitin-specific Protease 9X (USP9X) as a Deubiquitinase Acting on Ubiquitin-Peroxin 5 (PEX5) Thioester Conjugate

“…In mammals, plants, and many other organisms, both PTS1-and PTS2-containing proteins are targeted to the organelle by PEX5, the socalled peroxisomal shuttling receptor (4 -7). The PEX5-PTS1 interaction is direct, whereas PTS2-containing proteins bind PEX5 via the adaptor protein PEX7 (8,9).…”