Model for the motor component of dynein heavy chain based on homology to the AAA family of oligomeric ATPases
Model for the motor component of dynein heavy chain based on homology to the AAA family of oligomeric ATPases
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DOI：
10.1016/s0969-2126(00)00557-8
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发表时间：
2001-02-07
期刊：
影响因子：
5.7
通讯作者：
Gibbons, IR
中科院分区：
文献类型：
--
作者：
Mocz, G;Gibbons, IR
背景资料：最近的迭代方法序列比对表明，动力蛋白的380 kDa的运动单位属于AAA类的伴侣蛋白样ATP酶。这些比对表明，380 kDa运动单元的核心包含一个由六个AAA模块组成的串联链，其中四个对应于先前描述的具有P环签名的ATP结合位点，两个是其中P环在进化中丢失的模块。我们报告了轴丝动力蛋白P重链中六个AAA模块的预测结构，基于它们与衍生自具有实验确定的结构的三种AAA蛋白的结构保守区的模板的同源性（PDB：1A 5 T，PDB：1DOO，和PDB：1 NSF）。动力蛋白中AAA模块的二级结构元件对应于在不同动力蛋白同种型中相对良好保守的序列区域。每个AAA模块的三级结构包含主要的α/β N结构域，较小的全α C结构域以一定角度突出，作为推定的核苷酸结合腔的一部分。六个模块的结构组装成一个环，直径约125埃，类似于通过电子显微镜观察到的动力蛋白电机unit.Conclusion的结构：预测的结构是支持的程序，评估全球，区域和本地的质量，与包含水解ATP结合位点的模块支持最强烈。动力蛋白马达与hsp 100伴侣蛋白家族中AAA模块的六聚体组装的结构相似性表明，动力蛋白沿着微管的ATP依赖性移位的基本机制可能与多肽的ATP依赖性移位有共同之处进入伴侣蛋白的内部隔室。
Background: Recent iterative methods for sequence alignment have indicated that the 380 kDa motor unit of dynein belongs to the AAA class of chaperone-like ATPases. These alignments indicate that the core of the 380 kDa motor unit contains a concatenated chain of six AAA modules, of which four correspond to the ATP binding sites with P-loop signatures described previously, and two are modules in which the P loop has been lost in evolution.Results: We report predicted structures for the six AAA modules in the P heavy chain of axonemal dynein, based upon their homology to a template of structurally conserved regions derived from three AAA proteins with experimentally determined structures (pdb:1A5T, pdb:1DOO, and pdb:1NSF). The secondary structural elements of the AAA modules in dynein correspond to regions of sequence that are relatively well conserved in different dynein isoforms. The tertiary structure of each AAA module comprises a major alpha/beta N domain from which a smaller all-alpha C domain protrudes at an angle, as part of the putative nucleotide binding cavity. The structures of the six modules are assembled into a ring, approximately 125 Angstrom in diameter, that resembles the structure of the dynein motor unit observed by electron microscopy.Conclusion: The predicted structures are supported by procedures that assess global, regional, and local quality, with the module containing the hydrolytic ATP binding site being supported the most strongly. The structural resemblance of the dynein motor to the hexameric assembly of AAA modules in the hsp100 family of chaperones suggests that the basic mechanism underlying the ATP-dependent translocation of dynein along a microtubule may have aspects in common with the ATP-dependent translocation of polypeptides into the interior compartment of chaperones.