TY  - JOUR
AU  - Chen, Walter W
AU  - Rodrigues, Tony A
AU  - Wendscheck, Daniel
AU  - Pedrosa, Ana G
AU  - Yang, Chendong
AU  - Francisco, Tânia
AU  - Möcklinghoff, Till
AU  - Zografakis, Alexandros
AU  - Nunes-Silva, Bernardo
AU  - Avraham, Reut E
AU  - Silva, Ana R
AU  - Ferreira, Maria J
AU  - Das, Hirak
AU  - Koster, Janet
AU  - Neuwirth, Simone
AU  - Bender, Julian
AU  - Oeljeklaus, Silke
AU  - Sondhi, Varun
AU  - Gatsogiannis, Christos
AU  - Schuldiner, Maya
AU  - Zalckvar, Einat
AU  - Hofmann, Kay
AU  - Waterham, Hans R
AU  - DeBerardinis, Ralph J
AU  - Azevedo, Jorge E
AU  - Warscheid, Bettina
TI  - PEX39 facilitates the peroxisomal import of PTS2-containing proteins.
JO  - Nature cell biology
VL  - 27
IS  - 8
SN  - 1465-7392
CY  - New York, NY
PB  - Nature America
M1  - DKFZ-2025-01603
SP  - 1256-1271
PY  - 2025
N1  - 2025 Aug;27(8):1256-1271
AB  - Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (also known as peroxins (PEXs)) cause devastating disease. PEX7 binds proteins containing a type 2 peroxisomal targeting signal (PTS2) to enable their import from the cytosol into peroxisomes, although many aspects of this process remain enigmatic. Utilizing in vitro assays, yeast and human cells, we show that PEX39, a previously uncharacterized protein, is a cytosolic peroxin that facilitates the import of PTS2-containing proteins by binding PEX7 and stabilizing its interaction with cargo proteins containing a PTS2. PEX39 and PEX13, a peroxisomal membrane translocon protein, both possess an (R/K)PWE motif necessary for PEX7 binding. Handover of PEX7 from PEX39 to PEX13 via these motifs provides a new paradigm for peroxisomal protein import and biogenesis. Collectively, this work reveals how PEX39 and (R/K)PWE motifs facilitate the import of PTS2-containing proteins and advances our understanding of peroxisomal disease.
LB  - PUB:(DE-HGF)16
C6  - pmid:40739340
DO  - DOI:10.1038/s41556-025-01711-z
UR  - https://inrepo02.dkfz.de/record/303258
ER  -