Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase.

Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase.
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DOI:
10.1038/nsmb.2317
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发表时间:
2012-06-10
影响因子:
16.8
通讯作者:
Cusack, Stephen
Cusack, Stephen
中科院分区:
生物学1区
文献类型:
--
作者:
Palencia, Andres;Crepin, Thibaut;Vu, Michael T.;Lincecum, Tommie L., Jr.;Martinis, Susan A.;Cusack, Stephen

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Leucyl-tRNA合成酶(LeuRS)通过协调将带错电荷的trna的3 '端从合成位点转移到单独的校对位点进行编辑,从而产生无错误的leucyl-tRNALeu。在这里,我们报道了大肠杆菌LeuRS- trnaleu复合物在氨基酰化或编辑构象中的共晶结构,并表明易位涉及四个灵活连接的LeuRS结构域的相关旋转。这使得tRNA能够将带电荷的tRNA 3 '端从封闭的氨基酰化状态引导到编辑位点。在氨基酰化过程中,编辑结构域出人意料地稳定了tRNA,而亮氨酸特异性结构域的大旋转定位了保守的KMSKS环,以结合tRNA的3 '端,促进催化作用。我们的结果为分子机器的结构动力学提供了新的见解,这对于精确的蛋白质合成是必不可少的。
Leucyl-tRNA synthetase (LeuRS) produces error free leucyl-tRNALeu by coordinating translocation of the 3′ end of (mis-)charged tRNAs from its synthetic site to a separate proof-reading site for editing. Here we report co-crystal structures of the Escherichia coli LeuRS-tRNALeu complex in the aminoacylation or editing conformations and show that translocation involves correlated rotations of four flexibly linked LeuRS domains. This pivots the tRNA to guide the charged tRNA 3′ end from the closed aminoacylation state to the editing site. The editing domain unexpectedly stabilizes the tRNA during aminoacylation while a large rotation of the leucine-specific domain positions the conserved KMSKS loop to bind the 3′ end of the tRNA, promoting catalysis. Our results give new insight into the structural dynamics of a molecular machine that is essential for accurate protein synthesis.
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