The first minutes in the life of a peroxisomal matrix protein

Abstract

In the field of intracellular protein sorting, peroxisomes are most famous by their capacity to import oligomeric proteins. The data supporting this remarkable property are abundant and, understandably, have inspired a variety of hypothetical models on how newly synthesized (cytosolic) proteins reach the peroxisome matrix. However, there is also accumulating evidence suggesting that many peroxisomal oligomeric proteins actually arrive at the peroxisome still as monomers. In support of this idea, recent data suggest that PEX5, the shuttling receptor for peroxisomal matrix proteins, is also a chaperone/holdase, binding newly synthesized peroxisomal proteins in the cytosol and blocking their oligomerization. Here we review the data behind these two different perspectives and discuss their mechanistic implications on this protein sorting pathway.

Protein transport into peroxisomes: Knowns and unknowns

“…The second was that most if not all peroxisomal proteins are imported into the organelle only after oligomerization in the cytosol , a generalization that is probably incorrect. Indeed, a growing number of observations suggest that many peroxisomal matrix proteins that are oligomeric in their native state actually arrive at the organelle matrix as monomers (reviewed in ). The reason for this does not seem to be simply a kinetic property of the protein transport system, with import of newly synthesized proteins occurring faster than their oligomerization in the cytosol.…”

“…Prospects & Overviews .... organelle matrix as monomers (reviewed in [40]). The reason for this does not seem to be simply a kinetic property of the protein transport system, with import of newly synthesized proteins occurring faster than their oligomerization in the cytosol.…”

Membrane topologies of PEX13 and PEX14 provide new insights on the mechanism of protein import into peroxisomes

“…An important one regards the DTM, the transmembrane protein complex through which newly synthesized PTS1 and PTS2 proteins are translocated into the peroxisome matrix. This complex has the remarkable capacity of accepting already folded proteins as substrates (reviewed in [34,35]), but our knowledge on its architecture is close to none. For instance, despite an abundance of data on protein-protein interactions involving DTM-components and their domains [13,14,[36][37][38][39][40][41][42][43][44][45][46][47][48][49], the different membrane topology models presently available for some of its components make any attempt to draw a coherent picture of this complex a difficult task [47,48,[50][51][52][53][54][55][56][57].…”

Subcellular Localization of a Plant Catalase-Phenol Oxidase, AcCATPO, from Amaranthus and Identification of a Non-canonical Peroxisome Targeting Signal

“…It is well known that the sorting of proteins to peroxisomes mainly depends on either of two types of signal sequences, PTS1 and PTS2 (see Rucktäschel et al, 2011 ; Baker et al, 2016 ; Erdmann, 2016 for reviews and references within). The PTS1 as the most common one, is a tripeptide present at the C-termini of proteins and frequently ends with the sequence S-K-L or its variants with a consensus sequence S/A/C-K/R/H-L/M ( Gould et al, 1989 ; Lametschwandtner et al, 1998 ; Brocard and Hartig, 2006 ; Williams et al, 2012 ; see Dias et al, 2016 ; Meinecke et al, 2016 for reviews and references within). In contrast to PTS1, the PTS2 functions at internal locations, with a conserved non-apeptide in the N-terminal domain, such as R-L-X5-H-L, and R/K-L/V/I-X5-H/Q-L/A (X: any amino acid) ( Terlecky et al, 1995 ; Petriv et al, 2004 ; see Baker et al, 2016 ; Meinecke et al, 2016 for reviews and references within).…”