4xfv
Crystal Structure of Elp2
Structural highlights
FunctionELP2_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. ELP2 is dispensable for the complex integrity and, in vitro, is not required for complex HAT activity. It is not required for the association of the complex with nascent RNA transcript. Independently, ELP2 may be involved in polarized exocytosis. 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 PubMedElongator is a highly conserved multiprotein complex composed of six subunits (Elp1-6). Elongator has been associated with various cellular activities and has attracted clinical attention because of its role in certain neurodegenerative diseases. Here, we present the crystal structure of the Elp2 subunit revealing two seven-bladed WD40 beta propellers, and show by structure-guided mutational analyses that the WD40 fold integrity of Elp2 is necessary for its binding to Elp1 and Elp3 subunits in multiple species. The detailed biochemical experiments indicate that Elp2 binds microtubules through its conserved alkaline residues in vitro and in vivo. We find that both the mutually independent Elp2-mediated Elongator assembly and the cytoskeleton association are important for yeast viability. In addition, mutation of Elp2 greatly affects the histone H3 acetylation activity of Elongator in vivo. Our results indicate that Elp2 is a necessary component for functional Elongator and acts as a hub in the formation of various complexes. The Elp2 Subunit Is Essential for Elongator Complex Assembly and Functional Regulation.,Dong C, Lin Z, Diao W, Li D, Chu X, Wang Z, Zhou H, Xie Z, Shen Y, Long J Structure. 2015 Apr 29. pii: S0969-2126(15)00122-7. doi:, 10.1016/j.str.2015.03.018. PMID:25960406[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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