The C-Ala domain brings together editing and aminoacylation functions on one tRNA.
Protein synthesis involves the accurate attachment of amino acids to their matching transfer RNA (tRNA) molecules. Mistranslating the amino acids serine or glycine for alanine is prevented by the function of independent but collaborative aminoacylation and editing domains of alanyl-tRNA synthetases (AlaRSs). We show that the C-Ala domain plays a key role in AlaRS function. The C-Ala domain is universally tethered to the editing domain both in AlaRS and in many homologous free-standing editing proteins. Crystal structure and functional analyses showed that C-Ala forms an ancient single-stranded nucleic acid binding motif that promotes cooperative binding of both aminoacylation and editing domains to tRNA(Ala). In addition, C-Ala may have played an essential role in the evolution of AlaRSs by coupling aminoacylation to editing to prevent mistranslation.
Guo
Min
M
The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chong
Yeeting E
YE
Beebe
Kirk
K
Shapiro
Ryan
R
Yang
Xiang-Lei
XL
Schimmel
Paul
P
D000412:Alanine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D001483:Base Sequence; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D012344:RNA, Transfer, Ala / Q000737:chemistry* / Q000378:metabolism*; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000378:metabolism; D046249:Transfer RNA Aminoacylation
D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012344:RNA, Transfer, Ala; D012346:RNA, Transfer, Amino Acyl; D000412:Alanine-tRNA Ligase