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Wobble base pair dictates tRNA fidelity

tRNA synthetases must attach the appropriate amino acid to the appropriate, cognate tRNA to maintain proper translation of the genetic code into protein. A single non-Watson–Crick base pair in the tRNA for alanine, G3·U70, ensures correct aminoacylation by the synthetase (AlaRS). Shigeyuki Yokoyama and colleagues report two crystal structures of AlaRS from the archaeon Archaeoglobus fulgidus, in complexes with tRNAAlabearing G3·U70 (tRNAAla/GU) and with a variant bearing A3·U70 (tRNAAla/AU), together with an alanyl-AMP analogue. Comparison of the structures reveals the basis for selectivity. The unique geometry of G3·U70 orients the CCA region of tRNA and guides the terminal adenosine into the catalytic site. This mechanism explains how a small number of nucleotides distant from the catalytic site can determine the reactivity of specific aminoacylation.

Nature Volume 510 Issue 7506

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