Cao Tingting, Sun Lingfei, Jiang Yuxiang, Huang Shanjin, Wang Jiawei, Chen Zhucheng
Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, P.R. China; School of Life Science, Tsinghua University, Beijing 100084, P.R. China;
School of Life Science, Tsinghua University, Beijing 100084, P.R. China;
Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):8985-90. doi: 10.1073/pnas.1602818113. Epub 2016 Jul 25.
Actin polymerizes and forms filamentous structures (F-actin) in the cytoplasm of eukaryotic cells. It also exists in the nucleus and regulates various nucleic acid transactions, particularly through its incorporation into multiple chromatin-remodeling complexes. However, the specific structure of actin and the mechanisms that regulate its polymeric nature inside the nucleus remain unknown. Here, we report the crystal structure of nuclear actin (N-actin) complexed with actin-related protein 4 (Arp4) and the helicase-SANT-associated (HSA) domain of the chromatin remodeler Swr1. The inner face and barbed end of N-actin are sequestered by interactions with Arp4 and the HSA domain, respectively, which prevents N-actin from polymerization and binding to many actin regulators. The two major domains of N-actin are more twisted than those of globular actin (G-actin), and its nucleotide-binding pocket is occluded, freeing N-actin from binding to and regulation by ATP. These findings revealed the salient structural features of N-actin that distinguish it from its cytoplasmic counterpart and provide a rational basis for its functions and regulation inside the nucleus.
肌动蛋白在真核细胞的细胞质中聚合形成丝状结构（F-肌动蛋白）。它也存在于细胞核中，并调节各种核酸相关活动，特别是通过整合到多种染色质重塑复合物中发挥作用。然而，肌动蛋白在细胞核内的具体结构以及调节其聚合性质的机制仍不清楚。在此，我们报道了与肌动蛋白相关蛋白4（Arp4）和染色质重塑因子Swr1的解旋酶-SANT相关（HSA）结构域复合的核肌动蛋白（N-肌动蛋白）的晶体结构。N-肌动蛋白的内表面和尖端分别通过与Arp4和HSA结构域的相互作用而被封闭，这阻止了N-肌动蛋白的聚合以及与许多肌动蛋白调节因子的结合。N-肌动蛋白的两个主要结构域比球状肌动蛋白（G-肌动蛋白）的结构域扭曲程度更大，并且其核苷酸结合口袋被封闭，使得N-肌动蛋白无法与ATP结合及受其调节。这些发现揭示了N-肌动蛋白与细胞质中的肌动蛋白不同的显著结构特征，并为其在细胞核内的功能和调节提供了合理依据。
