Structural and mechanistic basis of pre- and posttransfer editing by leucyl-tRNA synthetase.
The aminoacyl-tRNA synthetases link tRNAs with their cognate amino acid. In some cases, their fidelity relies on hydrolytic editing that destroys incorrectly activated amino acids or mischarged tRNAs. We present structures of leucyl-tRNA synthetase complexed with analogs of the distinct pre- and posttransfer editing substrates. The editing active site binds the two different substrates using a single amino acid discriminatory pocket while preserving the same mode of adenine recognition. This suggests a similar mechanism of hydrolysis for both editing substrates that depends on a key, completely conserved aspartic acid, which interacts with the alpha-amino group of the noncognate amino acid and positions both substrates for hydrolysis. Our results demonstrate the economy by which a single active site accommodates two distinct substrates in a proofreading process critical to the fidelity of protein synthesis.
Lincecum
Tommie L
TL
Department of Biology and Biochemistry, University of Houston, Texas 77204, USA.
Tukalo
Michael
M
Yaremchuk
Anna
A
Mursinna
Richard S
RS
Williams
Amy M
AM
Sproat
Brian S
BS
Van Den Eynde
Wendy
W
Link
Andreas
A
Van Calenbergh
Serge
S
Grøtli
Morten
M
Martinis
Susan A
SA
Cusack
Stephen
S
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D007935:Leucine-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D008968:Molecular Conformation; D014176:Protein Biosynthesis / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D046911:Macromolecular Substances; D011506:Proteins; D001224:Aspartic Acid; D012343:RNA, Transfer; D007935:Leucine-tRNA Ligase; D000241:Adenosine