Skowyra Michael L, Rapoport Tom A
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Cell Biol. 2025 May 9. doi: 10.1038/s41556-025-01662-5.
Most proteins imported into peroxisomes use a carboxy-terminal PTS1 signal, which is recognized by soluble receptors that transport the cargo through a nuclear pore-like conduit in the peroxisomal membrane formed by the tyrosine and glycine-rich YG domain of PEX13. The receptors then return to the cytosol through a separate retrotranslocon. Some peroxisomal proteins instead use an amino-terminal PTS2 signal that is recognized by an adaptor called PEX7, but how they are imported is poorly understood. Here we show that PTS2 cargo is moved through the YG phase by PEX7 bound to a receptor. After cargo release inside peroxisomes, PEX7 returns to the cytosol by moving back on its own through the YG phase. The chaperone PEX39 then extracts PEX7 from the phase on the cytosolic side and helps to reload PEX7 with a new receptor and cargo to start another import cycle. Our results provide a comprehensive model of PTS2 protein import.
大多数导入过氧化物酶体的蛋白质使用羧基末端PTS1信号，该信号由可溶性受体识别，这些受体通过由PEX13富含酪氨酸和甘氨酸的YG结构域形成的过氧化物酶体膜中的核孔样通道运输货物。然后，受体通过一个单独的逆向转运通道返回细胞质。相反，一些过氧化物酶体蛋白使用氨基末端PTS2信号，该信号由一种名为PEX7的衔接蛋白识别，但它们如何被导入却知之甚少。在这里，我们表明PTS2货物通过与受体结合的PEX7在YG相中移动。货物在过氧化物酶体内部释放后，PEX7通过自身在YG相中反向移动返回细胞质。然后伴侣蛋白PEX39从细胞质一侧的相中提取PEX7，并帮助PEX7重新装载新的受体和货物，以开始另一个导入循环。我们的结果提供了一个PTS2蛋白导入的全面模型。
