Methylation of ciliary dynein motors involves the essential cytosolic assembly factor DNAAF3/PF22.
Methylation of ciliary dynein motors involves the essential cytosolic assembly factor DNAAF3/PF22.
复制标题
纤毛动力蛋白马达的甲基化涉及必需的胞质组装因子 DNAAF3/PF22。
DOI：
10.1073/pnas.2318522121
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发表时间：
2024
影响因子：
11.1
通讯作者：
King,StephenM
中科院分区：
文献类型：
--
作者：
Sakato-Antoku,Miho;Patel-King,RamilaS;Balsbaugh,JeremyL;King,StephenM
轴丝动力蛋白马达驱动纤毛运动，并且可以由多达20种不同的组分组成，其组合质量为~2 MDa。在哺乳动物中，动力蛋白在轴丝上部结构内组装的失败导致原发性纤毛运动障碍。综合征表型包括不孕症、鼻炎、严重支气管疾病和内脏逆位。19个特定的胞质因子（动力蛋白轴丝组装因子; DNAAFs）是轴丝动力蛋白组装所必需的，尽管所涉及的详细机制仍然非常不清楚。在这里，我们确定了必要的组装因子DNAAF 3作为S-腺苷甲硫氨酸依赖性甲基转移酶的结构直系同源物。我们证明，动力蛋白重链，特别是那些形成纤毛外臂，甲基化的关键残基内的各种核苷酸结合位点和微管结合结构域螺旋直接参与过渡到低结合亲和力。这些可变的修饰，这通常是缺失的DNAAF 3直系同源物PF 22（DAB 1）的衣原体空突变体，可能会影响运动机械化学微调个别动力蛋白复合物的活动。
Axonemal dynein motors drive ciliary motility and can consist of up to twenty distinct components with a combined mass of ~2 MDa. In mammals, failure of dyneins to assemble within the axonemal superstructure leads to primary ciliary dyskinesia. Syndromic phenotypes include infertility, rhinitis, severe bronchial conditions, and situs inversus. Nineteen specific cytosolic factors (Dynein Axonemal Assembly Factors; DNAAFs) are necessary for axonemal dynein assembly, although the detailed mechanisms involved remain very unclear. Here, we identify the essential assembly factor DNAAF3 as a structural ortholog of S-adenosylmethionine–dependent methyltransferases. We demonstrate that dynein heavy chains, especially those forming the ciliary outer arms, are methylated on key residues within various nucleotide-binding sites and on microtubule-binding domain helices directly involved in the transition to low binding affinity. These variable modifications, which are generally missing in aChlamydomonasnull mutant for the DNAAF3 ortholog PF22 (DAB1), likely impact on motor mechanochemistry fine-tuning the activities of individual dynein complexes.