The Elp2 Subunit Is Essential for Elongator Complex Assembly and Functional Regulation

• Published in: Structure (London) Vol. 23; no. 6; pp. 1078 - 1086
• Main Authors: Dong, Chunming, Lin, Zhijie, Diao, Wentao, Li, Dan, Chu, Xinlei, Wang, Zheng, Zhou, Hao, Xie, Zhiping, Shen, Yuequan, Long, Jiafu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 02.06.2015
• Subjects: Amino Acid Sequence; HEK293 Cells; Humans; Immunoblotting; Immunoprecipitation; Microtubule Proteins - metabolism; Microtubule-Associated Proteins - chemistry; Microtubule-Associated Proteins - metabolism; Models, Molecular; Molecular Sequence Data; Multiprotein Complexes - metabolism; Protein Binding; Protein Structure, Tertiary; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2015.03.018

Elongator 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 β 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. [Display omitted] •The structure of the WD40 domains in Elp2 consists of two seven-bladed β propellers•Elp2 binds to microtubules via its conserved alkaline residues•The WD40 fold integrity of Elp2 is essential for the Elongator complex assembly•Elp2 acting as a hub for various complexes formation is crucial for yeast viability Elongator complex (Elp1–6) plays vital roles in gene regulation. Dong et al. show that the Elp2 subunit folds into a two seven-bladed β-propeller structure, which is important for Elongator assembly and microtubules association, and highlight that Elp2 functions as a hub for formation of various complexes.