Multiple targeting modules on peroxisomal proteins are not redundant: discrete functions of targeting signals within Pmp47 and Pex8p.
Multiple targeting modules on peroxisomal proteins are not redundant: discrete functions of targeting signals within Pmp47 and Pex8p.
复制标题
过氧化物酶体蛋白上的多个靶向模块并不是多余的：Pmp47 和 Pex8p 内靶向信号的离散功能。
DOI：
10.1091/mbc.e03-11-0810
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发表时间：
2004
影响因子：
3.3
通讯作者：
Goodman,JoelM
中科院分区：
文献类型：
--
作者：
Wang,Xiaodong;McMahon,MoiraA;Shelton,SharyN;Nampaisansuk,Mongkol;Ballard,JohnathanL;Goodman,JoelM
几种过氧化物酶体蛋白具有两个不重叠的靶向信号。这些信号被称为“冗余”，因为仅用一个信号仍然可以实现靶向。我们现在报道 Pmp47 和 Pex8 内的单独靶向基序提供了互补功能。 Pmp47 是一种 ATP 易位蛋白，包含六个跨膜结构域 (TMD)。我们之前已经证明，TMD2 区域（称为 TMD2R，由 TMD2 和胞质环的短相邻片段组成）是靶向酿酒酵母中增殖的过氧化物酶体所必需的。我们现在报告说，类似的 TMD4R 不能靶向增殖的过氧化物酶体，但在仅含有基础（即非增殖）过氧化物酶体的细胞中至少同样或更好（取决于菌株和生长条件）。这些数据表明过氧化物酶体群体之间的靶向途径存在差异。 Pex8p是一种面向基质的外周蛋白，含有一个典型的羧基末端靶向序列（PTS1），该序列已被证明对于靶向而言不是必需的，表明存在第二个靶向结构域（尚未在酿酒酵母中定义）；因此，它的功能是未知的。我们表明，使用 PTS1 时，靶向基础过氧化物酶体而不是增殖的过氧化物酶体比不使用 PTS1 更有效。我们的结果表明，过氧化物酶体蛋白内的多个靶向信号扩大了过氧化物酶体异质群体之间的覆盖范围，并提高了某些代谢状态下的靶向效率。
Several peroxisomal proteins have two nonoverlapping targeting signals. These signals have been termed “redundant” because targeting can still occur with only one signal. We now report that separate targeting motifs within both Pmp47 and Pex8 provide complementary function. Pmp47 is an ATP translocator that contains six transmembrane domains (TMDs). We had previously shown that the TMD2 region (termed TMD2R, consisting of TMD2 and a short adjacent segment of cytosolic loop) was required for targeting to proliferated peroxisomes inSaccharomyces cerevisiae. We now report that the analogous TMD4R, which cannot target to proliferated peroxisomes, targets at least as well, or much better (depending on strain and growth conditions) in cells containing only basal (i.e., nonproliferated) peroxisomes. These data suggest differences in the targeting pathway among peroxisome populations. Pex8p, a peripheral protein facing the matrix, contains a typical carboxy terminal targeting sequence (PTS1) that has been shown to be nonessential for targeting, indicating the existence of a second targeting domain (not yet defined inS. cerevisiae); thus, its function was unknown. We show that targeting to basal peroxisomes, but not to proliferated peroxisomes, is more efficient with the PTS1 than without it. Our results indicate that multiple targeting signals within peroxisomal proteins extend coverage among heterogeneous populations of peroxisomes and increase efficiency of targeting in some metabolic states.