The C-Ala Domain Brings Together Editing and Aminoacylation Functions on One tRNA
Min Guo,
Yeeting E. Chong,
Kirk Beebe,*
Ryan Shapiro,
Xiang-Lei Yang,
Paul Schimmel
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.
* Present address: Metabolon, Incorporated, 800 Capitola Drive, Suite 1, Durham, NC 27713, USA.
To whom correspondence should be addressed. E-mail: schimmel{at}scripps.edu
