Structural insights into species-specific features of the ribosome from the human pathogen Mycobacterium tuberculosis.

Structural insights into species-specific features of the ribosome from the human pathogen Mycobacterium tuberculosis.
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DOI:
10.1093/nar/gkx785
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发表时间:
2017-10-13
影响因子:
14.9
通讯作者:
Zhang J
Zhang J
中科院分区:
生物学2区
文献类型:
--
作者:
Yang K;Chang JY;Cui Z;Li X;Meng R;Duan L;Thongchol J;Jakana J;Huwe CM;Sacchettini JC;Zhang J

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结核分枝杆菌(Mtb)的核糖体具有物种特异性核糖体RNA(rRNA)扩展片段和核糖体蛋白(rProtein)。在这里,我们提出了近原子结构的结核分枝杆菌50 S核糖体亚基和完整的结核分枝杆菌70 S核糖体,解决了冷冻电子显微镜。在连接大小核糖体亚基后,Mtb 23 S rRNA的一个100-nt长的扩展片段,命名为H54 a或“B”,将与rRNA螺旋H68和rProtein uL 2的相互作用转换为与rProtein bS 6的相互作用,形成一个新的亚基间桥“B 9”。在Mtb 70 S中,桥B 9大部分被维持,导致手柄、L1柄和小亚基在旋转和非旋转状态下的相关运动。在解码中心和肽基转移酶中心附近分别发现了两个新的蛋白质密度。这些结果为研究结核分枝杆菌的翻译以及开发新的结核药物提供了结构基础。
Ribosomes from Mycobacterium tuberculosis (Mtb) possess species-specific ribosomal RNA (rRNA) expansion segments and ribosomal proteins (rProtein). Here, we present the near-atomic structures of the Mtb 50S ribosomal subunit and the complete Mtb 70S ribosome, solved by cryo-electron microscopy. Upon joining of the large and small ribosomal subunits, a 100-nt long expansion segment of the Mtb 23S rRNA, named H54a or the ‘handle’, switches interactions from with rRNA helix H68 and rProtein uL2 to with rProtein bS6, forming a new intersubunit bridge ‘B9’. In Mtb 70S, bridge B9 is mostly maintained, leading to correlated motions among the handle, the L1 stalk and the small subunit in the rotated and non-rotated states. Two new protein densities were discovered near the decoding center and the peptidyl transferase center, respectively. These results provide a structural basis for studying translation in Mtb as well as developing new tuberculosis drugs.
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