Gardner Brooke M, Chowdhury Saikat, Lander Gabriel C, Martin Andreas
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA; Miller Institute for Basic Research in Science, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Mol Biol. 2015 Mar 27;427(6 Pt B):1375-1388. doi: 10.1016/j.jmb.2015.01.019. Epub 2015 Feb 7.
Pex1 and Pex6 are Type-2 AAA+ ATPases required for the de novo biogenesis of peroxisomes. Mutations in Pex1 and Pex6 account for the majority of the most severe forms of peroxisome biogenesis disorders in humans. Here, we show that the ATP-dependent complex of Pex1 and Pex6 from Saccharomyces cerevisiae is a heterohexamer with alternating subunits. Within the Pex1/Pex6 complex, only the D2 ATPase ring hydrolyzes ATP, while nucleotide binding in the D1 ring promotes complex assembly. ATP hydrolysis by Pex1 is highly coordinated with that of Pex6. Furthermore, Pex15, the membrane anchor required for Pex1/Pex6 recruitment to peroxisomes, inhibits the ATP-hydrolysis activity of Pex1/Pex6.
Pex1和Pex6是过氧化物酶体从头生物合成所必需的2型AAA+ATP酶。Pex1和Pex6的突变导致了人类过氧化物酶体生物合成障碍最严重形式的大多数情况。在此，我们表明来自酿酒酵母的Pex1和Pex6的ATP依赖性复合物是一种具有交替亚基的异源六聚体。在Pex1/Pex6复合物中，只有D2 ATP酶环水解ATP，而D1环中的核苷酸结合促进复合物组装。Pex1的ATP水解与Pex6的ATP水解高度协调。此外，Pex15是Pex1/Pex6被募集到过氧化物酶体所必需的膜锚定蛋白，它抑制Pex1/Pex6的ATP水解活性。
