Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
Traffic. 2019 Jul;20(7):504-515. doi: 10.1111/tra.12652. Epub 2019 May 27.
Most soluble proteins targeted to the peroxisomal matrix contain a C-terminal peroxisome targeting signal type 1 (PTS1) or an N-terminal PTS2 that is recognized by the receptors Pex5p and Pex7p, respectively. These receptors cycle between the cytosol and peroxisome and back again for multiple rounds of cargo delivery to the peroxisome. A small number of peroxisomal matrix proteins, including all six isozymes of peroxisomal fatty acyl-CoA oxidase (Aox) of the yeast Yarrowia lipolytica, contain neither a PTS1 nor a PTS2. Pex20p has been shown to function as a co-receptor for Pex7p in the import of PTS2 cargo into peroxisomes. Here we show that cells of Y. lipolytica deleted for the PEX20 gene fail to import not only the PTS2-containing protein 3-ketoacyl-CoA thiolase (Pot1p) but also the non-PTS1/non-PTS2 Aox isozymes. Pex20p binds directly to Aox isozymes Aox3p and Aox5p, which requires the C-terminal Wxxx(F/Y) motif of Pex20p. A W411G mutation in the C-terminal Wxxx(F/Y) motif causes Aox isozymes to be mislocalized to the cytosol. Pex20p interacts physically with members of the peroxisomal import docking complex, Pex13p and Pex14p. Our results are consistent with a role for Pex20p as the receptor for import of the non-PTS1/non-PTS2 Aox isozymes into peroxisomes.
大多数靶向过氧化物酶体基质的可溶性蛋白含有一个 C 末端过氧化物酶体靶向信号类型 1（PTS1）或一个 N 末端 PTS2，分别被受体 Pex5p 和 Pex7p 识别。这些受体在细胞质和过氧化物酶体之间循环，并再次进行多次货物传递到过氧化物酶体。少数过氧化物酶体基质蛋白，包括酵母解脂耶氏酵母的六个体脂酰辅酶 A 氧化酶（Aox）同工酶，既不含有 PTS1 也不含有 PTS2。已经表明 Pex20p 在 PTS2 货物进入过氧化物酶体的导入中作为 Pex7p 的共受体起作用。在这里，我们表明，PEX20 基因缺失的 Y. lipolytica 细胞不仅不能导入含有 PTS2 的 3-酮酰基辅酶 A 硫解酶（Pot1p），而且不能导入非 PTS1/非 PTS2 Aox 同工酶。Pex20p 直接与 Aox 同工酶 Aox3p 和 Aox5p 结合，这需要 Pex20p 的 C 末端 Wxxx(F/Y)基序。C 末端 Wxxx(F/Y)基序中的 W411G 突变导致 Aox 同工酶错误定位到细胞质中。Pex20p 与过氧化物酶体导入对接复合物的成员 Pex13p 和 Pex14p 物理相互作用。我们的结果与 Pex20p 作为非 PTS1/非 PTS2 Aox 同工酶导入过氧化物酶体的受体的作用一致。
