Three-dimensional structure of human tubulin chaperone cofactor A
Three-dimensional structure of human tubulin chaperone cofactor A
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DOI：
10.1016/s0022-2836(02)00185-7
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发表时间：
2002-05-10
影响因子：
5.6
通讯作者：
Coll, M
中科院分区：
文献类型：
--
作者：
Guasch, A;Aloria, K;Coll, M
α 和 β-微管蛋白在一系列分子伴侣辅助步骤中折叠。至少有五种蛋白质辅助因子参与伴侣蛋白后微管蛋白折叠途径，并需要维持微管蛋白的供应；其中一些还参与微管动力学。在微管蛋白折叠途径中发现的第一个微管蛋白伴侣是辅因子 A (CoA)。在这里，我们描述了通过多波长反常衍射 (MAD) 确定的 1.7 埃分辨率的人类 CoA 的三维结构。该结构是一种棒状单体，由三α螺旋束或卷曲螺旋组成，第二个螺旋由脯氨酸断裂扭结，在蛋白质的一个面上提供了凸面。螺旋通过短转连接，其中一个位于 α2 和 α3 之间，包括 3(10) 螺旋。肽图分析和肽竞争实验表明，CoA 通过三个 α 螺旋区域与 β-微管蛋白相互作用，但不与杆端环相互作用。主要相互作用发生在杆凸面上的中间扭结 a2 螺旋上。发现与 Hsp70 伴侣辅助因子 BAG 结构域具有很强的 3D 结构同源性，表明这些蛋白质定义了一个具有简单紧凑结构的辅助因子家族。 α-血影蛋白/α-肌动蛋白重复序列发现了进一步的结构同源性，它们都是具有相同长度的十个螺旋圈的杆。我们建议将这些三螺旋束称为阿尔法十模块。 (C) 2002 Elsevier Science Ltd. 保留所有权利。
alpha and beta-Tubulin fold in a series of chaperone-assisted steps. At least five protein cofactors are involved in the post-chaperonin tubulin folding pathway and required to maintain the supply of tubulin; some of them also participate in microtubule dynamics. The first tubulin chaperone identified in the tubulin folding pathway was cofactor A (CoA). Here we describe the three-dimensional structure of human CoA at 1.7 Angstrom resolution, determined by multiwavelength anomalous diffraction (MAD). The structure is a monomer with a rod-like shape and consists of a three-alpha-helix bundle, or coiled coil, with the second helix kinked by a proline break, offering a convex surface at one face of the protein. The helices are connected by short turns, one of them, between alpha2 and alpha3, including a 3(10)-helix. Peptide mapping analysis and competition experiments with peptides show that CoA interacts with beta-tubulin via the three alpha-helical regions but not with the rod-end loops. The main interaction occurs with the middle kinked a2 helix, at the convex face of the rod. Strong 3D structural homology is found with the Hsp70 chaperone cofactor BAG domain, suggesting that these proteins define a family of cofactors of simple compact architecture. Further structural homology is found with alpha-spectrin/ alpha-actinin repeats, all are rods of identical length of ten helical turns. We propose to call these three-helix bundles alpha ten modules. (C) 2002 Elsevier Science Ltd. All rights reserved.