The selective tRNA aminoacylation mechanism based on a single G•U pair

Masahiro Naganuma, Shun-ichi Sekine, Yeeting Esther Chong, Min Guo, Xiang-Lei Yang, Howard Gamper, Ya-Ming Hou, Paul Schimmel and Shigeyuki Yokoyama ()
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Masahiro Naganuma: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan
Shun-ichi Sekine: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan
Yeeting Esther Chong: The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Min Guo: The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Xiang-Lei Yang: The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Howard Gamper: Thomas Jefferson University
Ya-Ming Hou: Thomas Jefferson University
Paul Schimmel: The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Shigeyuki Yokoyama: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan

Nature, 2014, vol. 510, issue 7506, 507-511

Abstract: Abstract Ligation of tRNAs with their cognate amino acids, by aminoacyl-tRNA synthetases, establishes the genetic code. Throughout evolution, tRNAAla selection by alanyl-tRNA synthetase (AlaRS) has depended predominantly on a single wobble base pair in the acceptor stem, G3•U70, mainly on the kcat level. Here we report the crystal structures of an archaeal AlaRS in complex with tRNAAla with G3•U70 and its A3•U70 variant. AlaRS interacts with both the minor- and the major-groove sides of G3•U70, widening the major groove. The geometry difference between G3•U70 and A3•U70 is transmitted along the acceptor stem to the 3′-CCA region. Thus, the 3′-CCA region of tRNAAla with G3•U70 is oriented to the reactive route that reaches the active site, whereas that of the A3•U70 variant is folded back into the non-reactive route. This novel mechanism enables the single wobble pair to dominantly determine the specificity of tRNA selection, by an approximate 100-fold difference in kcat.

Date: 2014
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DOI: 10.1038/nature13440

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