title: The Elp2 subunit is essential for elongator complex assembly and functional regulation.
abstract: 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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Diao
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China. Electronic address: yuequan74@yahoo.com.
authors.forename: Yuequan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address: jflong@nankai.edu.cn.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Long
mesh_terms: D000595:Amino Acid Sequence; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008868:Microtubule Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C000605610:ELP2 protein, S cerevisiae; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins