Ast Julia, Bäcker Nils, Bittner Elena, Martorana Domenica, Ahmad Humda, Bölker Michael, Freitag Johannes
Department of Biology, Philipps-University Marburg, Marburg, Germany.
Institute of Metabolism and Systems Research (IMSR), and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, United Kingdom.
Front Cell Dev Biol. 2022 May 12;10:858084. doi: 10.3389/fcell.2022.858084. eCollection 2022.
Peroxisomes are dynamic multipurpose organelles with a major function in fatty acid oxidation and breakdown of hydrogen peroxide. Many proteins destined for the peroxisomal matrix contain a -terminal peroxisomal targeting signal type 1 (PTS1), which is recognized by tetratricopeptide repeat (TPR) proteins of the Pex5 family. Various species express at least two different Pex5 proteins, but how this contributes to protein import and organelle function is not fully understood. Here, we analyzed truncated and chimeric variants of two Pex5 proteins, Pex5a and Pex5b, from the fungus Both proteins are required for optimal growth on oleic acid-containing medium. The -terminal domain (NTD) of Pex5b is critical for import of all investigated peroxisomal matrix proteins including PTS2 proteins and at least one protein without a canonical PTS. In contrast, the NTD of Pex5a is not sufficient for translocation of peroxisomal matrix proteins. In the presence of Pex5b, however, specific cargo can be imported this domain of Pex5a. The TPR domains of Pex5a and Pex5b differ in their affinity to variations of the PTS1 motif and thus can mediate import of different subsets of matrix proteins. Together, our data reveal that employs versatile targeting modules to control peroxisome function. These findings will promote our understanding of peroxisomal protein import also in other biological systems.
过氧化物酶体是动态的多功能细胞器，在脂肪酸氧化和过氧化氢分解中起主要作用。许多定位于过氧化物酶体基质的蛋白质含有一个C端1型过氧化物酶体靶向信号（PTS1），该信号由Pex5家族的四肽重复（TPR）蛋白识别。不同物种至少表达两种不同的Pex5蛋白，但这如何促进蛋白质导入和细胞器功能尚不完全清楚。在这里，我们分析了来自真菌的两种Pex5蛋白Pex5a和Pex5b的截短和嵌合变体。两种蛋白都是在含油酸培养基上最佳生长所必需的。Pex5b的N端结构域（NTD）对于所有研究的过氧化物酶体基质蛋白的导入至关重要，包括PTS2蛋白和至少一种没有典型PTS的蛋白。相比之下，Pex5a的NTD不足以转运过氧化物酶体基质蛋白。然而，在存在Pex5b的情况下，特定货物可以通过Pex5a的这个结构域导入。Pex5a和Pex5b的TPR结构域对PTS1基序变体的亲和力不同，因此可以介导不同基质蛋白子集的导入。总之，我们的数据表明，该真菌采用通用的靶向模块来控制过氧化物酶体功能。这些发现也将促进我们对其他生物系统中过氧化物酶体蛋白导入的理解。
