Li Shanshan, Hsieh Kan-Yen, Kuo Chiao-I, Lee Szu-Hui, Pintilie Grigore D, Zhang Kaiming, Chang Chung-I
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale and Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
Department of Bioengineering and James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
Sci Adv. 2021 Oct 15;7(42):eabj7835. doi: 10.1126/sciadv.abj7835.
Lon is an evolutionarily conserved proteolytic machine carrying out a wide spectrum of biological activities by degrading misfolded damaged proteins and specific cellular substrates. Lon contains a large N-terminal domain and forms a hexameric core of fused adenosine triphosphatase and protease domains. Here, we report two complete structures of Lon engaging a substrate, determined by cryo–electron microscopy to 2.4-angstrom resolution. These structures show a multilayered architecture featuring a tensegrity triangle complex, uniquely constructed by six long N-terminal helices. The interlocked helix triangle is assembled on the top of the hexameric core to spread a web of six globular substrate-binding domains. It serves as a multipurpose platform that controls the access of substrates to the AAA+ ring, provides a ruler-based mechanism for substrate selection, and acts as a pulley device to facilitate unfolding of the translocated substrate. This work provides a complete framework for understanding the structural mechanisms of Lon.
Lon是一种进化上保守的蛋白水解机器，通过降解错误折叠的受损蛋白和特定的细胞底物来执行广泛的生物活性。Lon包含一个大的N端结构域，并形成一个由融合的三磷酸腺苷酶和蛋白酶结构域组成的六聚体核心。在这里，我们报告了Lon与底物结合的两个完整结构，通过冷冻电子显微镜确定其分辨率为2.4埃。这些结构显示出一种多层结构，其特征是一个张拉整体三角形复合体，由六个长的N端螺旋独特构建而成。互锁的螺旋三角形组装在六聚体核心的顶部，以展开由六个球状底物结合结构域组成的网络。它作为一个多功能平台，控制底物进入AAA+环，提供基于尺子的底物选择机制，并作为一个滑轮装置促进转运底物的展开。这项工作为理解Lon的结构机制提供了一个完整的框架。
