Abstract of the PDB Structure's related Publication:
The evolutionarily conserved Elongator complex, which is composed of six subunits elongator protein 1 (Elp1 to -6), plays vital roles in gene regulation. The molecular hallmark of familial dysautonomia (FD) is the splicing mutation of Elp1 [also known as IκB kinase complex-associated protein (IKAP)] in the nervous system that is believed to be the primary cause of the devastating symptoms of this disease. Here, we demonstrate that disease-related mutations in Elp1 affect Elongator assembly, and we have determined the structure of the C-terminal portion of human Elp1 (Elp1-CT), which is sufficient for full-length Elp1 dimerization, as well as the structure of the cognate dimerization domain of yeast Elp1 (yElp1-DD). Our study reveals that the formation of the Elp1 dimer contributes to its stability in vitro and in vivo and is required for the assembly of both the human and yeast Elongator complexes. Functional studies suggest that Elp1 dimerization is essential for yeast viability. Collectively, our results identify the evolutionarily conserved dimerization domain of Elp1 and suggest that the pathological mechanisms underlying the onset and progression of Elp1 mutation-related disease may result from impaired Elongator activities.
One of the six protein cofactors required for the synthesis of 5-carboxymethyl group (cm5) on the wobble uridine-34 of a few tRNA. Acetate or acetyl-CoA is the donor of acetyl group, but the detailed mechanism of the reaction is still unknown. The cm5U derivative is the intermediate for further biochemical transformation of U34 derivative to either 5-methoxycarbonylmethyl uridine (mcm5U) catalysed by Trm9/Trm112 or 5-carbamoylmethyluridine (ncm5U) catalysed by a still unknown enzyme. Mutation in Elp (especially Elp3) influences telomeric gene silencing and DNA damage response. The multi-subunit complex El1-6 also interacts with elongating RNA polymerase II (RNAPII) is thought to facilitate transcription through histone acetylation.
A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae.