Fujiki Yukio, Miyata Non, Matsumoto Naomi, Tamura Shigehiko
Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka 812-8581, Japan.
Biochem Soc Trans. 2008 Feb;36(Pt 1):109-13. doi: 10.1042/BST0360109.
The peroxisome is a single-membrane-bound organelle found in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient PBDs (peroxisome biogenesis disorders), such as Zellweger syndrome. Two AAA (ATPase associated with various cellular activities) peroxins, Pex1p and Pex6p, are encoded by PEX1 and PEX6, the causal genes for CG (complementation group) 1 and CG4 PBDs respectively. PEX26, which is responsible for CG8 PBDs, codes for Pex26p, the recruiter of Pex1p-Pex6p complexes to peroxisomes. We recently assigned the binding regions between human Pex1p and Pex6p and elucidated the pivotal roles that the AAA cassettes, D1 and D2 domains, play in Pex1p-Pex6p interaction and in peroxisome biogenesis. ATP binding to both AAA cassettes of Pex1p and Pex6p was a prerequisite for the Pex1p-Pex6p interaction and peroxisomal localization, but ATP hydrolysis by the D2 domains was not required. Pex1p exists in two distinct oligomeric forms, a homo-oligomer in the cytosol and a hetero-oligomer on peroxisome membranes, with these possibly having distinct functions in peroxisome biogenesis. AAA peroxins are involved in the export from peroxisomes of Pex5p, the PTS1 (peroxisome-targeting signal type 1) receptor.
过氧化物酶体是真核生物中一种由单层膜包裹的细胞器。过氧化物酶体缺乏症（如泽尔韦格综合征等过氧化物酶体生物发生障碍）凸显了过氧化物酶体在人类中的功能重要性。两种AAA（与多种细胞活动相关的ATP酶）过氧化物酶蛋白，Pex1p和Pex6p，分别由PEX1和PEX6编码，它们是互补组1和互补组4过氧化物酶体生物发生障碍的致病基因。负责互补组8过氧化物酶体生物发生障碍的PEX26编码Pex26p，它是Pex1p - Pex6p复合物募集到过氧化物酶体的因子。我们最近确定了人类Pex1p和Pex6p之间的结合区域，并阐明了AAA结构域、D1和D2结构域在Pex1p - Pex6p相互作用和过氧化物酶体生物发生中所起的关键作用。ATP与Pex1p和Pex6p的两个AAA结构域结合是Pex1p - Pex6p相互作用和过氧化物酶体定位的先决条件，但D2结构域的ATP水解并非必需。Pex1p以两种不同的寡聚形式存在，一种是胞质中的同型寡聚体，另一种是过氧化物酶体膜上的异型寡聚体，它们可能在过氧化物酶体生物发生中具有不同的功能。AAA过氧化物酶蛋白参与了过氧化物酶体靶向信号1（PTS1）受体Pex5p从过氧化物酶体的输出过程。
