必需核糖体组装 AAA-ATP 酶 Rix7 的冷冻电镜结构。
Cryo-EM structure of the essential ribosome assembly AAA-ATPase Rix7.
机构信息
Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
出版信息
Nat Commun. 2019 Jan 31;10(1):513. doi: 10.1038/s41467-019-08373-0.
Rix7 is an essential type II AAA-ATPase required for the formation of the large ribosomal subunit. Rix7 has been proposed to utilize the power of ATP hydrolysis to drive the removal of assembly factors from pre-60S particles, but the mechanism of release is unknown. Rix7's mammalian homolog, NVL2 has been linked to cancer and mental illness disorders, highlighting the need to understand the molecular mechanisms of this essential machine. Here we report the cryo-EM reconstruction of the tandem AAA domains of Rix7 which form an asymmetric stacked homohexameric ring. We trapped Rix7 with a polypeptide in the central channel, revealing Rix7's role as a molecular unfoldase. The structure establishes that type II AAA-ATPases lacking the aromatic-hydrophobic motif within the first AAA domain can engage a substrate throughout the entire central channel. The structure also reveals that Rix7 contains unique post-α7 insertions within both AAA domains important for Rix7 function.
Rix7 是一种必需的 II 型 AAA-ATPase，对于大亚基核糖体的形成至关重要。有人提出，Rix7 利用 ATP 水解的能量驱动组装因子从预 60S 颗粒中释放，但释放的机制尚不清楚。Rix7 的哺乳动物同源物 NVL2 与癌症和精神疾病有关，这凸显了理解这一基本机器的分子机制的必要性。在这里，我们报告了串联 AAA 结构域的冷冻电镜重构，这些结构域形成了不对称堆叠的同六聚体环。我们用多肽捕获了 Rix7 ，揭示了 Rix7 作为分子解折叠酶的作用。该结构确定了缺乏第一个 AAA 结构域内芳香族疏水性基序的 II 型 AAA-ATPase 可以通过整个中央通道与底物结合。该结构还表明，Rix7 在两个 AAA 结构域中都含有独特的α7 后插入片段，这对于 Rix7 的功能很重要。
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