The crystal structure of yeast mitochondrial ThrRS in complex with the canonical threonine tRNA
- Univ. of Illinois, Chicago, IL (United States)
- Univ. of Texas, Houston, TX (United States)
In mitochondria of Saccharomyces cerevisiae, a single aminoacyl-tRNA synthetase (aaRS), MST1, aminoacylates two isoacceptor tRNAs, tRNA1Thr and tRNA2Thr, 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 tRNA2Thr 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 tRNA1Thr.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Inst. of Health; NCI; NIGMS
- Grant/Contract Number:
- AC02-06CH11357; R01 GM097042; R01 GM115431; ACB-12002; AGM-12006
- OSTI ID:
- 1252770
- Journal Information:
- Nucleic Acids Research, Vol. 44, Issue 3; ISSN 0305-1048
- Publisher:
- Oxford University PressCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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