德国弗莱堡大学Bettina Warscheid小组的一项最新研究的论文发现了PEX39促进含有PTS2蛋白的过氧化物酶体的输入。相关论文发表在2025年7月30日出版的《自然—细胞生物学》杂志上。

通过酵母和人类细胞的体外实验，研究人员发现PEX39是一种细胞质过氧化物，通过结合PEX7促进含有PTS2的蛋白质的进口，并稳定其与含有PTS2的货物蛋白的相互作用。PEX39和PEX13是一种过氧化物酶体膜转位蛋白，它们都具有PEX7结合所必需的（R/K）PWE基序。通过这些基序将PEX7从PEX39转移到PEX13，为过氧化物酶体蛋白的输入和生物发生提供了新的范式。总的来说，这项工作揭示了PEX39和（R/K）PWE基序如何促进含有PTS2的蛋白质的输入，并促进了他们对过氧化物酶体疾病的理解。

据了解，过氧化物酶体是人体健康所必需的代谢细胞器。过氧化物酶体生物发生蛋白（也称为过氧化物蛋白（PEXs））缺陷是一种毁灭性疾病。PEX7结合含有2型过氧化物酶体靶向信号（PTS2）的蛋白质，使其从细胞质进入过氧化物酶体，尽管这一过程的许多方面仍然是谜。

附：英文原文

Title: PEX39 facilitates the peroxisomal import of PTS2-containing proteins

Author: Chen, Walter W., Rodrigues, Tony A., Wendscheck, Daniel, Pedrosa, Ana G., Yang, Chendong, Francisco, Tnia, Mcklinghoff, Till, Zografakis, Alexandros, Nunes-Silva, Bernardo, Avraham, Reut E., Silva, Ana R., Ferreira, Maria J., Das, Hirak, Koster, Janet, Neuwirth, Simone, Bender, Julian, Oeljeklaus, Silke, Sondhi, Varun, Gatsogiannis, Christos, Schuldiner, Maya, Zalckvar, Einat, Hofmann, Kay, Waterham, Hans R., DeBerardinis, Ralph J., Azevedo, Jorge E., Warscheid, Bettina

Issue&Volume: 2025-07-30

Abstract: 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.

DOI: 10.1038/s41556-025-01711-z

Source: https://www.nature.com/articles/s41556-025-01711-z