Structural and Biochemical Insights into the Assembly of the DPY-30/Ash2L Heterotrimer

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Title: Structural and Biochemical Insights into the Assembly of the DPY-30/Ash2L Heterotrimer
Authors: Haddad, John
Date: 2017
Embargo: 2018-09-13
Abstract: In eukaryotes, the SET1 family of methyltransferases carry out the methylation of Lysine 4 on Histone H3. Alone, these enzymes exhibit low enzymatic activity and require the presence of additional regulatory proteins, which include RbBP5, Ash2L, WDR5 and DPY-30, to stimulate their catalytic activity. While previous structural studies established the structural basis underlying the interaction between RbBP5, Ash2L and WDR5, the formation of the Ash2L/DPY-30 complex remains elusive. Here we report the crystal structure of the Ash2L/DPY-30 complex solved at 2.2Å. Our results show that a Cterminal amphipathic α-helix on Ash2L makes several hydrophobic interactions with the DPY-30 homodimer. Moreover, the structure reveals that a tryptophan residue on Ash2L, which directly precedes its C-terminal amphipathic α-helix, makes key interactions with one of DPY-30 α-helix. Finally, biochemical studies of Ash2L revealed a hitherto unknown ability of this protein to bind anionic lipids.
URL: http://hdl.handle.net/10393/36616
http://dx.doi.org/10.20381/ruor-20896
CollectionThèses, 2011 - // Theses, 2011 -
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