5CQS

Dimerization of Elp1 is essential for Elongator complex assembly

5CQS の概要

• エントリーDOI: 10.2210/pdb5cqs/pdb
• 関連するPDBエントリー: 5CQR
• 分子名称: Elongator complex protein 1 (2 entities in total)
• 機能のキーワード: familial dysautonomia, elongator complex, elp1 subunit, dimerization, protein binding
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 200905.95

構造登録者

Lin, Z.,Xu, H.,Li, F.,Diao, W.,Long, J.,Shen, Y. (登録日: 2015-07-22, 公開日: 2015-08-19, 最終更新日: 2024-11-13)

主引用文献

Xu, H.,Lin, Z.,Li, F.,Diao, W.,Dong, C.,Zhou, H.,Xie, X.,Wang, Z.,Shen, Y.,Long, J.
Dimerization of elongator protein 1 is essential for Elongator complex assembly.
Proc.Natl.Acad.Sci.USA, 112:10697-10702, 2015

PubMed Abstract: 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.

PubMed: 26261306
DOI: 10.1073/pnas.1502597112

実験手法

X-RAY DIFFRACTION (2.7 Å)