The crystal structure of yeast .... tRNA.pdf (4.5 MB)

The crystal structure of yeast mitochondrial ThrRS in complex with the canonical threonine tRNA

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journal contribution
posted on 29.08.2016 by K. M. Holman, J. Wu, J. Q. Ling, M. Simonovi
In mitochondria of Saccharomyces cerevisiae, a single aminoacyl- TRNA synthetase (aaRS), MST1, aminoacylates two isoacceptor tRNAs, tRNA1 Thr and tRNA2 Thr, that harbor anticodon loops of different size and sequence. As a result of this promiscuity, reassignment of the CUN codon box from leucine to threonine is facilitated. However, the mechanism by which a single aaRS binds distinct anticodon loops with high specificity is not well understood. Herein, we present the crystal structure of MST1 in complex with the canonical tRNA2 Thr and non-hydrolyzable analog of threonyl adenylate. Our structure reveals that the dimeric arrangement of MST1 is essential for binding the 5′-phosphate, the second base pair of the acceptor stem, the first two base pairs of the anticodon stem and the first nucleotide of the variable arm. Further, in contrast to the bacterial ortholog that 'reads' the entire anticodon sequence, MST1 recognizes bases in the second and third position and the nucleotide upstream of the anticodon sequence. We speculate that a flexible loop linking strands β4 and β5 may be allosteric regulator that establishes cross-subunit communication between the aminoacylation and tRNA-binding sites. We also propose that structural features of the anticodon-binding domain in MST1 permit binding of the enlarged anticodon loop of tRNA2 Thr.

Funding

National Institute of General Medical Sciences of the National Institutes of Health [R01 GM097042 to M.S. and R01 GM115431 to J.L.]; U.S. DOE [under Contract No.DE-AC02-06CH11357 to Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory]; GM/CA@APS (23ID-D and 23BM) sector has been funded from the NCI (ACB- 12002) and NIGMS (AGM-12006). Funding for open access charge: National Institute of General Medical Sciences of the National Institutes of Health [R01 GM097042 to M.S.].

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Publisher Statement

This is a copy of an article published in Nucleic Acids Research. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Publisher

Oxford University Press

Language

en_US

issn

0305-1048

Issue date

01/01/2015

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