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Dual‐mode recognition of noncanonical tRNAs Ser by seryl‐tRNA synthetase in mammalian mitochondria
Author(s) -
Chimnaronk Sarin,
Gravers Jeppesen Mads,
Suzuki Tsutomu,
Nyborg Jens,
Watanabe Kimitsuna
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600811
Subject(s) - biology , mitochondrion , transfer rna , dual mode , dual (grammatical number) , genetics , aminoacyl trna synthetase , microbiology and biotechnology , biochemistry , gene , rna , art , literature , engineering , aerospace engineering
The secondary structures of metazoan mitochondrial (mt) tRNAs Ser deviate markedly from the paradigm of the canonical cloverleaf structure; particularly, tRNA Ser GCU corresponding to the AG Y codon ( Y =U and C) is highly truncated and intrinsically missing the entire dihydrouridine arm. None of the mt serine isoacceptors possesses the elongated variable arm, which is the universal landmark for recognition by seryl‐tRNA synthetase (SerRS). Here, we report the crystal structure of mammalian mt SerRS from Bos taurus in complex with seryl adenylate at an atomic resolution of 1.65 Å. Coupling structural information with a tRNA‐docking model and the mutagenesis studies, we have unraveled the key elements that establish tRNA binding specificity, differ from all other known bacterial and eukaryotic systems, are the characteristic extensions in both extremities, as well as a few basic residues residing in the amino‐terminal helical arm of mt SerRS. Our data further uncover an unprecedented mechanism of a dual‐mode recognition employed to discriminate two distinct ‘bizarre’ mt tRNAs Ser by alternative combination of interaction sites.