舒林将轴丝外动力蛋白臂包装用于纤毛靶向。
Shulin packages axonemal outer dynein arms for ciliary targeting.
机构信息
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Bioanalytics, Institute of Biotechnology, Technische Universität Berlin, 13355 Berlin, Germany.
出版信息
Science. 2021 Feb 26;371(6532):910-916. doi: 10.1126/science.abe0526.
Abstract
The main force generators in eukaryotic cilia and flagella are axonemal outer dynein arms (ODAs). During ciliogenesis, these ~1.8-megadalton complexes are assembled in the cytoplasm and targeted to cilia by an unknown mechanism. Here, we used the ciliate to identify two factors (Q22YU3 and Q22MS1) that bind ODAs in the cytoplasm and are required for ODA delivery to cilia. Q22YU3, which we named Shulin, locked the ODA motor domains into a closed conformation and inhibited motor activity. Cryo-electron microscopy revealed how Shulin stabilized this compact form of ODAs by binding to the dynein tails. Our findings provide a molecular explanation for how newly assembled dyneins are packaged for delivery to the cilia.
摘要
真核纤毛和鞭毛中的主要力发生器是轴丝外动力蛋白臂（ODA）。在纤毛发生过程中，这些约 1800 万道尔顿的复合物在细胞质中组装，并通过未知的机制靶向纤毛。在这里，我们使用纤毛虫 来鉴定两种因子（Q22YU3 和 Q22MS1），它们在细胞质中结合 ODA，并需要将 ODA 递送到纤毛。我们将 Q22YU3 命名为 Shulin，它将 ODA 的马达结构域锁定在关闭构象中，并抑制了马达活性。冷冻电镜揭示了 Shulin 如何通过与动力蛋白尾部结合来稳定这种紧凑形式的 ODA。我们的发现为新组装的动力蛋白如何被包装以递送到纤毛提供了分子解释。
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