Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine.
Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine.
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DOI：
10.1016/j.cell.2009.09.034
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发表时间：
2009-11-13
期刊：
影响因子：
64.5
通讯作者：
Sauer RT
中科院分区：
文献类型：
--
作者：
Glynn SE;Martin A;Nager AR;Baker TA;Sauer RT
ClpX是AAA+机器，其使用ATP结合和水解的能量来解折叠天然蛋白质并将解折叠的多肽易位到ClpP肽酶中。这里呈现的晶体结构揭示了无核苷酸和核苷酸结合的ClpX的环六聚体的显著不对称性。不对称性是由单个亚基的大AAA+结构域和小AAA+结构域之间的旋转变化引起的。这些差异阻止核苷酸结合到两个亚基，产生交错排列的ClpX亚基和孔环周围的六聚体环，并提供了一种机制，耦合由ATP结合或水解引起的构象变化在一个亚基弯曲运动的整个环。我们的结构解释了许多解决方案的ClpX功能的研究，预测不规则多肽易位过程中的孔弹性机制，并建议如何重复的构象变化可能耦合到机械工作在ATP酶循环的ClpX和相关的分子机器。
ClpX is a AAA+ machine that uses the energy of ATP binding and hydrolysis to unfold native proteins and translocate unfolded polypeptides into the ClpP peptidase. The crystal structures presented here reveal striking asymmetry in ring hexamers of nucleotide-free and nucleotide-bound ClpX. Asymmetry arises from large changes in rotation between the large and small AAA+ domains of individual subunits. These differences prevent nucleotide binding to two subunits, generate a staggered arrangement of ClpX subunits and pore loops around the hexameric ring, and provide a mechanism for coupling conformational changes caused by ATP binding or hydrolysis in one subunit to flexing motions of the entire ring. Our structures explain numerous solution studies of ClpX function, predict mechanisms for pore elasticity during translocation of irregular polypeptides, and suggest how repetitive conformational changes might be coupled to mechanical work during the ATPase cycle of ClpX and related molecular machines.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
10.5
作者：
Gottesman, S;Roche, E;Sauer, RT
通讯作者：
Sauer, RT
影响因子：
16
作者：
Kim, YI;Burton, RE;Baker, TA
通讯作者：
Baker, TA
影响因子：
3
作者：
Diemand, Alexander V.;Lupas, Andrei N.
通讯作者：
Lupas, Andrei N.
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL