5cqs | pdb_00005cqs
Dimerization of Elp1 is essential for Elongator complex assembly
Structural highlights
FunctionELP1_YEAST Acts as component of the RNA polymerase II elongator complex, which is a major histone acetyltransferase component of the RNA polymerase II (RNAPII) holoenzyme and is involved in transcriptional elongation. Association with elongating RNAPII requires a hyperphosphorylated state of the RNAPII C-terminal domain (CTD). Elongator binds to both naked and nucleosomal DNA, can acetylate both core and nucleosomal histones, and is involved in chromatin remodeling. It acetylates histones H3, preferentially at 'Lys-14', and H4, preferentially at 'Lys-8'. It functions as a gamma-toxin target (TOT); disruption of the complex confers resistance to Kluyveromyces lactis toxin zymocin (pGKL1 killer toxin). May also be involved in sensitiviy to Pichia inositovora toxin. May be involved in tRNA modification. Independently, ELP3 may be involved in polarized exocytosis. It is required for the polarized localization of GTPase-activating protein SEC2. Is required for an early step in synthesis of 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups present on uridines at the wobble position in tRNA.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedThe 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 IkappaB 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. Dimerization of elongator protein 1 is essential for Elongator complex assembly.,Xu H, Lin Z, Li F, Diao W, Dong C, Zhou H, Xie X, Wang Z, Shen Y, Long J Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10697-702. doi:, 10.1073/pnas.1502597112. Epub 2015 Aug 10. PMID:26261306[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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