Identification of the TRiC/CCT substrate binding sites uncovers the function of subunit diversity in eukaryotic chaperonins.
Identification of the TRiC/CCT substrate binding sites uncovers the function of subunit diversity in eukaryotic chaperonins.
复制标题
DOI：
10.1016/j.molcel.2006.09.003
复制
发表时间：
2006-10
期刊：
影响因子：
16
通讯作者：
Christoph Spiess;Erik J. Miller;A. J. McClellan;J. Frydman
中科院分区：
文献类型：
--
作者：
Christoph Spiess;Erik J. Miller;A. J. McClellan;J. Frydman
环状异寡聚体伴侣蛋白trc/CCT使用三磷酸腺苷折叠真核蛋白质的不同子集。为了确定TRIC/CCT底物识别的基础，我们将伴侣蛋白与VHL肿瘤抑制因子的相互作用进行了映射。VHL有两个明确的TICE结合决定因素。每个决定簇都与伴侣蛋白亚基的一个特定子集相联系，这表明对偶联蛋白表现出截然不同但重叠的特异性。这些亚基中的底物结合位点位于顶端结构域中的螺旋区，在结构上与细菌伴侣蛋白的螺旋区域相同。在TRIC亚基之间转移螺旋11的远端部分足以转移给定底物基序的特异性。我们得出结论，底物结合域的结构在真核生物和细菌伴侣蛋白中进化上是保守的。结合TIRE底物的特异性和可塑性的独特组合可能使这种伴侣蛋白识别的基序范围多样化，并有助于其折叠真核蛋白质的独特能力。
The ring-shaped hetero-oligomeric chaperonin TRiC/CCT uses ATP to fold a diverse subset of eukaryotic proteins. To define the basis of TRiC/CCT substrate recognition, we mapped the chaperonin interactions with the VHL tumor suppressor. VHL has two well-defined TRiC binding determinants. Each determinant contacts a specific subset of chaperonin subunits, indicating that TRiC paralogs exhibit distinct but overlapping specificities. The substrate binding site in these subunits localizes to a helical region in the apical domains that is structurally equivalent to that of bacterial chaperonins. Transferring the distal portion of helix 11 between TRiC subunits suffices to transfer specificity for a given substrate motif. We conclude that the architecture of the substrate binding domain is evolutionarily conserved among eukaryotic and bacterial chaperonins. The unique combination of specificity and plasticity in TRiC substrate binding may diversify the range of motifs recognized by this chaperonin and contribute to its unique ability to fold eukaryotic proteins.