Tubulin subunits exist in an activated conformational state generated and maintained by protein cofactors.
Tubulin subunits exist in an activated conformational state generated and maintained by protein cofactors.
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DOI：
10.1083/jcb.138.4.821
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发表时间：
1997-08-25
期刊：
影响因子：
--
通讯作者：
Cowan NJ
中科院分区：
文献类型：
--
作者：
Tian G;Lewis SA;Feierbach B;Stearns T;Rommelaere H;Ampe C;Cowan NJ
体外天然α/β微管蛋白异二聚体的产生取决于胞浆伴侣蛋白和几种蛋白辅因子的作用。我们先前表明，四个这样的辅因子（称为A，C，D和E）与天然微管蛋白一起作用于由伴侣蛋白产生的β-微管蛋白折叠中间体，以产生可聚合的微管蛋白异二聚体。然而，这组辅因子仅非常低效地从由相同伴侣蛋白产生的α-微管蛋白折叠中间体产生天然异源二聚体。在这里，我们描述了一种新的微管蛋白折叠辅因子（辅因子B）的分离，表征和遗传分析，它大大提高了体外α-微管蛋白折叠的效率。这使得对α-和β-微管蛋白折叠的综合研究成为可能：我们发现导致天然α-和β-微管蛋白形成的途径收敛于α亚基的折叠需要含有β亚基的辅因子复合物的参与，反之亦然。我们还表明，天然α-或β-微管蛋白的螯合与辅因子的复合物形成的结果在剩余的游离亚基的不稳定和衰变。这些数据表明，微管蛋白折叠辅因子通过将α-和β-微管蛋白多肽置于和/或维持在形成天然α/β异二聚体所需的活化构象状态来发挥功能，并暗示每个亚基提供了另一个亚基正确折叠所需的信息。
The production of native α/β tubulin heterodimer in vitro depends on the action of cytosolic chaperonin and several protein cofactors. We previously showed that four such cofactors (termed A, C, D, and E) together with native tubulin act on β-tubulin folding intermediates generated by the chaperonin to produce polymerizable tubulin heterodimers. However, this set of cofactors generates native heterodimers only very inefficiently from α-tubulin folding intermediates produced by the same chaperonin. Here we describe the isolation, characterization, and genetic analysis of a novel tubulin folding cofactor (cofactor B) that greatly enhances the efficiency of α-tubulin folding in vitro. This enabled an integrated study of α- and β-tubulin folding: we find that the pathways leading to the formation of native α- and β-tubulin converge in that the folding of the α subunit requires the participation of cofactor complexes containing the β subunit and vice versa. We also show that sequestration of native α-or β-tubulins by complex formation with cofactors results in the destabilization and decay of the remaining free subunit. These data demonstrate that tubulin folding cofactors function by placing and/or maintaining α-and β-tubulin polypeptides in an activated conformational state required for the formation of native α/β heterodimers, and imply that each subunit provides information necessary for the proper folding of the other.
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DOI：
10.1073/pnas.91.19.9111
发表时间：
1994-09-13
影响因子：
11.1
作者：
CHEN, XY;SULLIVAN, DS;HUFFAKER, TC
通讯作者：
HUFFAKER, TC
影响因子：
11.4
作者：
FRYDMAN, J;NIMMESGERN, E;HARTL, FU
通讯作者：
HARTL, FU
影响因子：
5.3
作者：
GAO, YI;VAINBERG, IE;COWAN, NJ
通讯作者：
COWAN, NJ
DOI：
10.1101/sqb.1995.060.01.048
发表时间：
1995-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Horwich, AL;Weissman, JS;Fenton, WA
通讯作者：
Fenton, WA
影响因子：
3.2
作者：
ITO, H;FUKUDA, Y;KIMURA, A
通讯作者：
KIMURA, A