Crystal structure of the open conformation of the mammalian chaperonin CCT in complex with tubulin
Crystal structure of the open conformation of the mammalian chaperonin CCT in complex with tubulin
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DOI：
10.1038/nsmb.1971
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发表时间：
2011-01-01
影响因子：
16.8
通讯作者：
Montoya, Guillermo
中科院分区：
文献类型：
--
作者：
Munoz, Ines G.;Yebenes, Hugo;Montoya, Guillermo
蛋白质折叠是由分子伴侣辅助的。CCT是一种1-丙二醛低聚物，由两个环组成，由八个不同的60 kDa亚基组成。这种伴侣蛋白调节重要蛋白质的折叠，包括肌动蛋白、α-微管蛋白和β-微管蛋白。我们使用5.5埃分辨率的电子密度图重建了CCT，它显示了在两个环的内腔中都有衬底。在这里，我们展示了这种纳米机器与微管蛋白络合物中开放构象的晶体结构，提供了关于它帮助微管蛋白折叠的机制的信息。结构表明，底物与CCT顶区和赤道区的环相互作用。ATP结合口袋的组织表明底物在腔内伸展。我们的数据为了解这种伴侣蛋白的功能提供了基础。
Protein folding is assisted by molecular chaperones. CCT (chaperonin containing TCP-1, or TRiC) is a 1-MDa oligomer that is built by two rings comprising eight different 60-kDa subunits. This chaperonin regulates the folding of important proteins including actin, alpha-tubulin and beta-tubulin. We used an electron density map at 5.5 angstrom resolution to reconstruct CCT, which showed a substrate in the inner cavities of both rings. Here we present the crystal structure of the open conformation of this nanomachine in complex with tubulin, providing information about the mechanism by which it aids tubulin folding. The structure showed that the substrate interacts with loops in the apical and equatorial domains of CCT. The organization of the ATP-binding pockets suggests that the substrate is stretched inside the cavity. Our data provide the basis for understanding the function of this chaperonin.