Pex1/Pex6复合物是一种具有交替且高度协调亚基的异源六聚体AAA+马达蛋白。
The Pex1/Pex6 complex is a heterohexameric AAA+ motor with alternating and highly coordinated subunits.
作者信息
Gardner Brooke M, Chowdhury Saikat, Lander Gabriel C, Martin Andreas
机构信息
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.
出版信息
J Mol Biol. 2015 Mar 27;427(6 Pt B):1375-1388. doi: 10.1016/j.jmb.2015.01.019. Epub 2015 Feb 7.
Abstract
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.
摘要
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。
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本文引用的文献
1
Mechanistic insights into the recycling machine of the SNARE complex.对SNARE复合体循环机制的深入理解。
Nature. 2015 Feb 5;518(7537):61-7. doi: 10.1038/nature14148. Epub 2015 Jan 12.
2
Mechanochemical basis of protein degradation by a double-ring AAA+ machine.双环 AAA+ 机器降解蛋白质的机械化学基础。
Nat Struct Mol Biol. 2014 Oct;21(10):871-5. doi: 10.1038/nsmb.2885. Epub 2014 Sep 7.
3
Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation.卷曲螺旋结构域的头对尾相互作用调节ClpB活性以及在蛋白质解聚过程中与Hsp70的协同作用。
Elife. 2014 Apr 30;3:e02481. doi: 10.7554/eLife.02481.
4
The p97-FAF1 protein complex reveals a common mode of p97 adaptor binding.p97-FAF1 蛋白复合物揭示了 p97 衔接子结合的一种常见模式。
J Biol Chem. 2014 Apr 25;289(17):12077-12084. doi: 10.1074/jbc.M114.559591. Epub 2014 Mar 11.
5
The peroxisomal receptor dislocation pathway: to the exportomer and beyond.过氧化物酶体受体易位途径：走向外核体和更远。
Biochimie. 2014 Mar;98:16-28. doi: 10.1016/j.biochi.2013.12.009. Epub 2013 Dec 15.
6
Reconstitution of the 26S proteasome reveals functional asymmetries in its AAA+ unfoldase.26S 蛋白酶体的重建揭示了其 AAA+ 解聚酶的功能不对称性。
Nat Struct Mol Biol. 2013 Oct;20(10):1164-72. doi: 10.1038/nsmb.2659. Epub 2013 Sep 8.
7
Peroxisome formation and maintenance are dependent on the endoplasmic reticulum.过氧化物酶体的形成和维持依赖于内质网。
Annu Rev Biochem. 2013;82:723-44. doi: 10.1146/annurev-biochem-081111-125123. Epub 2013 Feb 14.
8
RELION: implementation of a Bayesian approach to cryo-EM structure determination.RELION：贝叶斯方法在低温电子显微镜结构测定中的应用。
J Struct Biol. 2012 Dec;180(3):519-30. doi: 10.1016/j.jsb.2012.09.006. Epub 2012 Sep 19.
9
ATP-dependent assembly of the heteromeric Pex1p-Pex6p-complex of the peroxisomal matrix protein import machinery.依赖于 ATP 的异源 Pex1p-Pex6p-复合物的组装，该复合物是过氧化物酶体基质蛋白导入机器的一部分。
J Struct Biol. 2012 Aug;179(2):126-32. doi: 10.1016/j.jsb.2012.06.002. Epub 2012 Jun 16.
10
Biochemically distinct vesicles from the endoplasmic reticulum fuse to form peroxisomes.内质网上具有不同生化性质的小泡融合形成过氧化物酶体。
Cell. 2012 Apr 13;149(2):397-409. doi: 10.1016/j.cell.2012.01.054.
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