Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolská 135, 61265 Brno, Czech Republic.
Nucleic Acids Res. 2010 Mar;38(4):1325-40. doi: 10.1093/nar/gkp1057. Epub 2009 Dec 1.
Helix 38 (H38) of the large ribosomal subunit, with a length of 110 A, reaches the small subunit through intersubunit bridge B1a. Previous cryo-EM studies revealed that the tip of H38 moves by more than 10 A from the non-ratcheted to the ratcheted state of the ribosome while mutational studies implicated a key role of flexible H38 in attenuation of translocation and in dynamical signaling between ribosomal functional centers. We investigate a region including the elbow-shaped kink-turn (Kt-38) in the Haloarcula marismortui archaeal ribosome, and equivalently positioned elbows in three eubacterial species, located at the H38 base. We performed explicit solvent molecular dynamics simulations on the H38 elbows in all four species. They are formed by at first sight unrelated sequences resulting in diverse base interactions but built with the same overall topology, as shown by X-ray crystallography. The elbows display similar fluctuations and intrinsic flexibilities in simulations indicating that the eubacterial H38 elbows are structural and dynamical analogs of archaeal Kt-38. We suggest that this structural element plays a pivotal role in the large motions of H38 and may act as fulcrum for the abovementioned tip motion. The directional flexibility inferred from simulations correlates well with the cryo-EM results.
核糖体大亚基的 110Å 长的 helix38（H38）通过亚基间桥 B1a 与小亚基相连。先前的 cryo-EM 研究表明，当核糖体从非棘轮状态向棘轮状态转变时，H38 的尖端移动超过 10Å，而突变研究则表明，柔性 H38 在易位衰减和核糖体功能中心之间的动力学信号传递中起着关键作用。我们研究了包括 Haloarcula marismortui 古菌核糖体中肘状扭结（Kt-38）在内的一个区域，以及三个真细菌物种中位于 H38 基部的等效肘状结构。我们对所有四个物种的 H38 肘状结构进行了显式溶剂分子动力学模拟。它们由乍一看不相关的序列组成，导致不同的碱基相互作用，但通过 X 射线晶体学显示出相同的整体拓扑结构。肘状结构在模拟中表现出相似的波动和固有柔韧性，表明真细菌 H38 肘状结构是古菌 Kt-38 的结构和动力学类似物。我们提出，这个结构元素在 H38 的大运动中起着关键作用，并可能作为上述尖端运动的枢轴。从模拟中推断出的定向柔韧性与 cryo-EM 结果很好地相关。
