Lopez-Fanarraga M, Avila J, Guasch A, Coll M, Zabala J C
Departamento de Biología Molecular-Unidad Asociada al Centro de Investigaciones Biológicas (CSIC), Universidad de Cantabria, Cardenal Herrera Oria s/n, Santander, 39011, Spain.
J Struct Biol. 2001 Aug;135(2):219-29. doi: 10.1006/jsbi.2001.4386.
The microtubule cytoskeleton consists of a highly organized network of microtubule polymers bound to their accessory proteins: microtubule-associated proteins, molecular motors, and microtubule-organizing proteins. The microtubule subunits are heterodimers composed of one alpha-tubulin polypeptide and one beta-tubulin polypeptide that should undergo a complex folding processing before they achieve a quaternary structure that will allow their incorporation into the polymer. Due to the extremely high protein concentration that exists at the cell cytoplasm, there are alpha- and beta-tubulin interacting proteins that prevent the unwanted interaction of these polypeptides with the surrounding protein pool during folding, thus allowing microtubule dynamics. Several years ago, the development of a nondenaturing electrophoretic technique made it possible to identify different tubulin intermediate complexes during tubulin biogenesis in vitro. By these means, the cytosolic chaperonin containing TCP-1 (CCT or TriC) and prefoldin have been demonstrated to intervene through tubulin and actin folding. Various other cofactors also identified along the alpha- and beta-tubulin postchaperonin folding route are now known to have additional roles in tubulin biogenesis such as participating in the synthesis, transport, and storage of alpha- and beta-tubulin. The future characterization of the tubulin-binding sites to these proteins, and perhaps other still unknown proteins, will help in the development of chemicals that could interfere with tubulin folding and thus modulating microtubule dynamics. In this paper, current knowledge of the above postchaperonin folding cofactors, which are in fact chaperones involved in tubulin heterodimer quaternary structure achievement, will be reviewed.
微管细胞骨架由高度组织化的微管聚合物网络组成，这些微管聚合物与其辅助蛋白结合：微管相关蛋白、分子马达和微管组织蛋白。微管亚基是由一个α-微管蛋白多肽和一个β-微管蛋白多肽组成的异二聚体，在形成允许它们并入聚合物的四级结构之前，它们需要经历复杂的折叠过程。由于细胞质中存在极高的蛋白质浓度，存在α-和β-微管蛋白相互作用蛋白，这些蛋白可防止这些多肽在折叠过程中与周围蛋白质库发生不必要的相互作用，从而实现微管动力学。几年前，一种非变性电泳技术的发展使得在体外微管蛋白生物发生过程中鉴定不同的微管蛋白中间复合物成为可能。通过这些方法，已证明含有TCP-1的胞质伴侣蛋白（CCT或TriC）和预折叠蛋白通过微管蛋白和肌动蛋白折叠发挥作用。现在已知沿着α-和β-微管蛋白伴侣蛋白后折叠途径鉴定出的各种其他辅助因子在微管蛋白生物发生中具有额外作用，例如参与α-和β-微管蛋白的合成、运输和储存。对这些蛋白质以及可能其他仍未知蛋白质的微管蛋白结合位点的未来表征，将有助于开发能够干扰微管蛋白折叠从而调节微管动力学的化学物质。在本文中，将综述上述伴侣蛋白后折叠辅助因子的当前知识，这些辅助因子实际上是参与微管蛋白异二聚体四级结构形成的伴侣蛋白。
